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igf2 protein  (R&D Systems)


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    R&D Systems igf2 protein
    Igf2 Protein, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 83 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 93 stars, based on 83 article reviews
    igf2 protein - by Bioz Stars, 2026-03
    93/100 stars

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    R&D Systems igf2 protein
    Igf2 Protein, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Sino Biological recombinant human igf2
    Lung cancer cells induced CAFs activation via <t>IGF2</t> secretion (A) mRNA levels of IGF2 in cells were detected by qPCR. (B) IGF2 concentrations in cell culture medium were detected by ELISA. (C) NFs were treated with IGF2 (50 and 100 ng/mL) for 24 h. Cell morphology was observed under a microscope. (D) NFs were treated with IGF2. α-SMA and FAP expressions were detected by western blotting. (E) NFs were treated with IGF2. Cell proliferation was examined by CCK-8 kit after 48 h. (F and G) NFs were treated with IGF2. NFs migration was detected by trans-well assay after 24 h. (H) NFs were treated with CM or CM + IGF2 neutralizing antibody. Cell morphology was observed under a microscope. (I) NFs were treated with CM or CM + IGF2 neutralizing antibody. α-SMA and FAP expressions were detected by western blotting. (J) NFs were treated with CM or CM + IGF2 neutralizing antibody, and IGF2 (100 ng/mL). Cell proliferation was examined by CCK-8 kit after 48 h. (K and L) NFs were treated with CM or CM + IGF2 neutralizing antibody. NFs migration was detected by trans-well assay after 24 h. (M) The effect of IGF2 knockdown by RNAi. (N) IGF2 expression was knocked down in lung cancer cells, and then the CM was collected and used to culture NFs. α-SMA and FAP expressions were detected by western blotting. (O and P) IGF2 expression was knocked down in lung cancer cells by RNAi, and then the CM was collected and used to culture NFs. NFs migration was detected by trans-well assay after 24 h. Ab, neutralizing antibody. Scale bar, 100 μm. Data represents the mean ± SD from three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 .
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    Novoprotein igf2 recombination protein cf61
    FGR induces hippocampal <t>Igf2</t> downregulation by DNA hypomethylation, and neuronal Igf2 deletion impairs synaptic plasticity. (A) qPCR analysis of Igf family mRNA levels in the hippocampi from 8‐week‐old NS and FGR mice. n = 6 mice in each group. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein levels in the hippocampi at Postnatal Day 1, 1, 4, 8 weeks from NS and FGR mice. n = 3 mice in each group. (D) Bisulfite methylation sequencing of ICR in the hippocampi from 8‐week‐old NS and FGR mice. n = 9 mice in each group. (E, F) qPCR analysis of H19 (E) and Dnmt1 (F) mRNA levels in the hippocampi of 8‐week‐old NS and FGR mice. n = 6 mice in each group. (G) WB analysis of IGF2 protein level in the hippocampi of Ctrl and IKO mice. n = 4 mice in each group. (H) LTP measurements were performed in the CA1 region of acute slices from Ctrl and IKO mice. n = 3 in each group. (I) Representative Golgi staining images of the hippocampal DG neurons from Ctrl and IKO mice. Scale bar, 100 μm. (J and K) Quantification of the dendritic branches (J) and total dendritic length (K) of the hippocampal DG neurons. n = 6 mice in each group, 4–5 neurons in each mouse. (L) Representative Golgi staining images of hippocampal DG neuronal dendritic spines. Scale bar, 5 μm. (M) Quantification of the dendritic spine density. n = 6 mice in each group, 4–5 spine pictures in each mouse. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (H) or unpaired Student's t ‐test (A, C–F, H, J, K, M). ** p < 0.01 and *** p < 0.001. See also Figures and .
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    Takeda igf2 mrna-binding protein 3
    FGR induces hippocampal <t>Igf2</t> downregulation by DNA hypomethylation, and neuronal Igf2 deletion impairs synaptic plasticity. (A) qPCR analysis of Igf family mRNA levels in the hippocampi from 8‐week‐old NS and FGR mice. n = 6 mice in each group. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein levels in the hippocampi at Postnatal Day 1, 1, 4, 8 weeks from NS and FGR mice. n = 3 mice in each group. (D) Bisulfite methylation sequencing of ICR in the hippocampi from 8‐week‐old NS and FGR mice. n = 9 mice in each group. (E, F) qPCR analysis of H19 (E) and Dnmt1 (F) mRNA levels in the hippocampi of 8‐week‐old NS and FGR mice. n = 6 mice in each group. (G) WB analysis of IGF2 protein level in the hippocampi of Ctrl and IKO mice. n = 4 mice in each group. (H) LTP measurements were performed in the CA1 region of acute slices from Ctrl and IKO mice. n = 3 in each group. (I) Representative Golgi staining images of the hippocampal DG neurons from Ctrl and IKO mice. Scale bar, 100 μm. (J and K) Quantification of the dendritic branches (J) and total dendritic length (K) of the hippocampal DG neurons. n = 6 mice in each group, 4–5 neurons in each mouse. (L) Representative Golgi staining images of hippocampal DG neuronal dendritic spines. Scale bar, 5 μm. (M) Quantification of the dendritic spine density. n = 6 mice in each group, 4–5 spine pictures in each mouse. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (H) or unpaired Student's t ‐test (A, C–F, H, J, K, M). ** p < 0.01 and *** p < 0.001. See also Figures and .
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    ALFARES Pharmaceuticals igf2 protein
    Diagram demonstrating the potential link between <t>IGF2</t> and spermatogenesis dysfunction. Blue arrows represent a decrease, red arrows represent an increase, solid arrows represent an effect on downstream factors, t-shaped arrows represent an inhibitory effect. IGF2, insulin-like growth factor 2; TNFα, tumor necrosis factor α; LPS, lipopolysaccharides; IL-6, interleukin-6; ROS, reactive oxygen species; ER, endoplasmic reticulum; T2DM, type II diabetes mellitus; IR, insulin resistance; GCs, germ cells.
    Igf2 Protein, supplied by ALFARES Pharmaceuticals, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Cusabio igf2 protein
    The insulin signaling pathway and cholesterol metabolism pathway in malignant hepatoblast‐like cells. A,B) Developmental trajectory of hepatocyte cells inferred by monocle2, colored by cell subtypes (A) and CNV levels (B). C) Representative signaling pathways during the developmental trajectory of hepatocyte cells inferred by monocle2. Heatmap showing the dynamic changes in gene expression along the pseudotime trajectory in branch 1 and branch 2. D) Gene set enrichment analysis (GSEA) of malignant HB‐like cells versus all hepatocyte cells in the indicated gene sets. ES, enrichment score; RM, ranked metric; NES, normalized enrichment score; FDR, false discovery rate. E. Heatmap of key gene expression related to the regulation of cholesterol metabolic process (GO: 0090181) and cellular response to insulin stimulus (GO: 0032869) in the three hepatocyte cell types. F) Violin plots showing INS, IGF1, <t>IGF2,</t> INSR, and IGF1R expression levels in the three hepatocyte cell populations. G) Representative IHC images of IGF2 staining of tissue sections. H) The expression levels of key proteins for the insulin signaling and cholesterol metabolic pathways in five pairs of hepatoblastoma and paracancerous tissues. I) Cholesterol concentrations were analyzed in primary hepatoblastoma tumors and paired paracancerous normal liver tissues. J) Lipid droplets (LDs) in primary hepatoblastoma tumors and paired paracancerous liver tissues were stained with BODIPY 493/503. K) BODIPY 493/503 and DUSP9 antibody co‐staining in primary hepatoblastoma tumors.
    Igf2 Protein, supplied by Cusabio, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Cusabio secretory protein igf2
    The insulin signaling pathway and cholesterol metabolism pathway in malignant hepatoblast‐like cells. A,B) Developmental trajectory of hepatocyte cells inferred by monocle2, colored by cell subtypes (A) and CNV levels (B). C) Representative signaling pathways during the developmental trajectory of hepatocyte cells inferred by monocle2. Heatmap showing the dynamic changes in gene expression along the pseudotime trajectory in branch 1 and branch 2. D) Gene set enrichment analysis (GSEA) of malignant HB‐like cells versus all hepatocyte cells in the indicated gene sets. ES, enrichment score; RM, ranked metric; NES, normalized enrichment score; FDR, false discovery rate. E. Heatmap of key gene expression related to the regulation of cholesterol metabolic process (GO: 0090181) and cellular response to insulin stimulus (GO: 0032869) in the three hepatocyte cell types. F) Violin plots showing INS, IGF1, <t>IGF2,</t> INSR, and IGF1R expression levels in the three hepatocyte cell populations. G) Representative IHC images of IGF2 staining of tissue sections. H) The expression levels of key proteins for the insulin signaling and cholesterol metabolic pathways in five pairs of hepatoblastoma and paracancerous tissues. I) Cholesterol concentrations were analyzed in primary hepatoblastoma tumors and paired paracancerous normal liver tissues. J) Lipid droplets (LDs) in primary hepatoblastoma tumors and paired paracancerous liver tissues were stained with BODIPY 493/503. K) BODIPY 493/503 and DUSP9 antibody co‐staining in primary hepatoblastoma tumors.
    Secretory Protein Igf2, supplied by Cusabio, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    R&D Systems insulin growth factor 2 igf2 protein
    Effects of <t>IGF2</t> knockdown in XF-iMSCs on Col6a1 -KO/NSG MuSC differentiation. a mRNA expression of IGF2 and PXDN . The mRNA expression level of each gene was analyzed using RT-qPCR in Ad-MSCs, BM-MSCs, and XF-iMSCs. Levels are shown relative to those in XF-iMSCs. Data are shown as the mean ± SD. b Concentration of IGF2 in the culture supernatants of Ad-MSCs, BM-MSCs, and XF-iMSCs as obtained using ELISA. Data are shown as the mean ± SD. c mRNA expression level and concentration of IGF2 in the culture on co-culture day 3. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after single culture or co-culture with XF-iMSC, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. e Total number of DAPI + /hLamin A/C- mouse myogenic cells 3 days after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. f Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations 3 days after co-culture. Data from three independent experiments are shown as the mean ± SD. g mRNA expression level and concentration of IGF2 in the culture on co-culture day 6. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. h Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after single culture or co-culture with XF-iMSCs, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. i, j Area of MHC + myotubes ( i ) and number of MHC + myotubes ( j ) with four or more nuclei on day 6 after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. co-cluture experiment: n = 6 (XF-iMSCs, XF-iMSC_ IGF2-KD and XF-iMSC_mock), n = 3 (single culture). qPCR and ELISA experiment: n = 2 (Ad-MSCs, BM-MSCs, XF-iMSCs)
    Insulin Growth Factor 2 Igf2 Protein, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    R&D Systems recombinant human igf ii
    Effects of <t>IGF2</t> knockdown in XF-iMSCs on Col6a1 -KO/NSG MuSC differentiation. a mRNA expression of IGF2 and PXDN . The mRNA expression level of each gene was analyzed using RT-qPCR in Ad-MSCs, BM-MSCs, and XF-iMSCs. Levels are shown relative to those in XF-iMSCs. Data are shown as the mean ± SD. b Concentration of IGF2 in the culture supernatants of Ad-MSCs, BM-MSCs, and XF-iMSCs as obtained using ELISA. Data are shown as the mean ± SD. c mRNA expression level and concentration of IGF2 in the culture on co-culture day 3. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after single culture or co-culture with XF-iMSC, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. e Total number of DAPI + /hLamin A/C- mouse myogenic cells 3 days after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. f Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations 3 days after co-culture. Data from three independent experiments are shown as the mean ± SD. g mRNA expression level and concentration of IGF2 in the culture on co-culture day 6. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. h Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after single culture or co-culture with XF-iMSCs, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. i, j Area of MHC + myotubes ( i ) and number of MHC + myotubes ( j ) with four or more nuclei on day 6 after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. co-cluture experiment: n = 6 (XF-iMSCs, XF-iMSC_ IGF2-KD and XF-iMSC_mock), n = 3 (single culture). qPCR and ELISA experiment: n = 2 (Ad-MSCs, BM-MSCs, XF-iMSCs)
    Recombinant Human Igf Ii, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    R&D Systems recombinant mouse igf2 protein
    Hippocampal administration of <t>recombinant</t> <t>IGF2</t> normalizes both memory consolidation and relative cfos expression in aged Tsc2 +/− mice. (a) Schematic overview of 7d NORT including IGF2 administration on day 2 within 2 h after second training phase. (b), 7d NORT approach of aged Tsc2 mutant mice 7 days after IGF2 injection showed a significant enhancement of memory consolidation measured as discrimination index compared to the PBS‐injected mutant mice (two tailed t test: P (baseline) = 5,89e‐9, n (WT) = 32, n ( Tsc2+/− ) = 34); p (PBS) = 0.0066, n (WT) = 13, n ( Tsc2 +/− ) = 11; p (IGF2) = 0.4433, n (WT) = 18, n ( Tsc2 +/− ) = 17. (c) Relative mRNA expression levels of cfos in the hippocampus of aged Tsc2 mutants after IGF2 administration compared to the control group. No significant difference in Tsc2 +/− mice compared to wildtype controls after IGF2 treatment (two‐tailed t test: p (PBS) = 0.0004, n (WT) = 4, n ( Tsc2 +/− ) = 7); p (IGF2) = 0.2329, n (WT) = 6, n ( Tsc2 +/− ) = 8. Values were normalized against Gapdh and are presented as mean ± SEM, * p < 0.05, *** p < 0.001. Quantification was performed using Excel.
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    Lung cancer cells induced CAFs activation via IGF2 secretion (A) mRNA levels of IGF2 in cells were detected by qPCR. (B) IGF2 concentrations in cell culture medium were detected by ELISA. (C) NFs were treated with IGF2 (50 and 100 ng/mL) for 24 h. Cell morphology was observed under a microscope. (D) NFs were treated with IGF2. α-SMA and FAP expressions were detected by western blotting. (E) NFs were treated with IGF2. Cell proliferation was examined by CCK-8 kit after 48 h. (F and G) NFs were treated with IGF2. NFs migration was detected by trans-well assay after 24 h. (H) NFs were treated with CM or CM + IGF2 neutralizing antibody. Cell morphology was observed under a microscope. (I) NFs were treated with CM or CM + IGF2 neutralizing antibody. α-SMA and FAP expressions were detected by western blotting. (J) NFs were treated with CM or CM + IGF2 neutralizing antibody, and IGF2 (100 ng/mL). Cell proliferation was examined by CCK-8 kit after 48 h. (K and L) NFs were treated with CM or CM + IGF2 neutralizing antibody. NFs migration was detected by trans-well assay after 24 h. (M) The effect of IGF2 knockdown by RNAi. (N) IGF2 expression was knocked down in lung cancer cells, and then the CM was collected and used to culture NFs. α-SMA and FAP expressions were detected by western blotting. (O and P) IGF2 expression was knocked down in lung cancer cells by RNAi, and then the CM was collected and used to culture NFs. NFs migration was detected by trans-well assay after 24 h. Ab, neutralizing antibody. Scale bar, 100 μm. Data represents the mean ± SD from three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 .

    Journal: iScience

    Article Title: Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

    doi: 10.1016/j.isci.2024.111269

    Figure Lengend Snippet: Lung cancer cells induced CAFs activation via IGF2 secretion (A) mRNA levels of IGF2 in cells were detected by qPCR. (B) IGF2 concentrations in cell culture medium were detected by ELISA. (C) NFs were treated with IGF2 (50 and 100 ng/mL) for 24 h. Cell morphology was observed under a microscope. (D) NFs were treated with IGF2. α-SMA and FAP expressions were detected by western blotting. (E) NFs were treated with IGF2. Cell proliferation was examined by CCK-8 kit after 48 h. (F and G) NFs were treated with IGF2. NFs migration was detected by trans-well assay after 24 h. (H) NFs were treated with CM or CM + IGF2 neutralizing antibody. Cell morphology was observed under a microscope. (I) NFs were treated with CM or CM + IGF2 neutralizing antibody. α-SMA and FAP expressions were detected by western blotting. (J) NFs were treated with CM or CM + IGF2 neutralizing antibody, and IGF2 (100 ng/mL). Cell proliferation was examined by CCK-8 kit after 48 h. (K and L) NFs were treated with CM or CM + IGF2 neutralizing antibody. NFs migration was detected by trans-well assay after 24 h. (M) The effect of IGF2 knockdown by RNAi. (N) IGF2 expression was knocked down in lung cancer cells, and then the CM was collected and used to culture NFs. α-SMA and FAP expressions were detected by western blotting. (O and P) IGF2 expression was knocked down in lung cancer cells by RNAi, and then the CM was collected and used to culture NFs. NFs migration was detected by trans-well assay after 24 h. Ab, neutralizing antibody. Scale bar, 100 μm. Data represents the mean ± SD from three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 .

    Article Snippet: Recombinant human IGF2 , Sino Biological , Cat#13032-HNAY.

    Techniques: Activation Assay, Cell Culture, Enzyme-linked Immunosorbent Assay, Microscopy, Western Blot, CCK-8 Assay, Migration, Knockdown, Expressing

    IGF2-induced autophagy mediated the effect of lung cancer cells on CAFs activation (A) NFs were treated with CM and then were stained with 0.5 μg/mL AO for 15 min. The acidic vesicular organelles (AVOs) formation was observed under a fluorescence microscope (scale bar, 20 μm). (B) NFs were treated with CM. The expression of LC-3II and ATG5 were detected by western blotting. (C) NFs were treated with IGF2 (50 or 100 mg/mL) for 24 h. The AVOs formation was examined by AO staining (scale bar, 20 μm). (D) NFs were treated with IGF2. The expression of LC-3II and ATG5 was detected by western blotting. (E) NFs were treated with IGF2 or IGF2 + 3-MA (5 mM). The AVOs formation was examined by AO staining (scale bar, 20 μm). (F) NFs were treated with IGF2 or IGF2 + 3-MA. Protein expressions were detected by western blotting. (G) NFs were treated with IGF2 or IGF2 + 3-MA. Cell proliferation was examined by CCK-8 kit after 48 h. (H and I) NFs were treated with IGF2 or IGF2+3-MA. NFs migration was detected by trans-well assay after 24 h (scale bar, 100 μm). (J) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. The AVOs formation was examined by AO staining (scale bar, 20 μm). (K) NFs were treated with CM, IGF2, and CM + IGF2 Ab. Protein expressions were detected by western blotting. (L) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. Cell proliferation was examined by CCK-8 kit after 48 h. (M and N) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. NFs migration was detected by trans-well assay after 24 h (scale bar, 100 μm). (O and P) NFs were treated with RAPA (100 nM); α-SMA and FAP expressions were detected by western blotting (scale bar, 20 μm). (Q and R) NFs were treated with RAPA; NFs migration was detected by trans-well assay after 24 h. Ab, neutralizing antibody (scale bar, 100 μm). Data represents the mean ± SD from three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 .

    Journal: iScience

    Article Title: Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

    doi: 10.1016/j.isci.2024.111269

    Figure Lengend Snippet: IGF2-induced autophagy mediated the effect of lung cancer cells on CAFs activation (A) NFs were treated with CM and then were stained with 0.5 μg/mL AO for 15 min. The acidic vesicular organelles (AVOs) formation was observed under a fluorescence microscope (scale bar, 20 μm). (B) NFs were treated with CM. The expression of LC-3II and ATG5 were detected by western blotting. (C) NFs were treated with IGF2 (50 or 100 mg/mL) for 24 h. The AVOs formation was examined by AO staining (scale bar, 20 μm). (D) NFs were treated with IGF2. The expression of LC-3II and ATG5 was detected by western blotting. (E) NFs were treated with IGF2 or IGF2 + 3-MA (5 mM). The AVOs formation was examined by AO staining (scale bar, 20 μm). (F) NFs were treated with IGF2 or IGF2 + 3-MA. Protein expressions were detected by western blotting. (G) NFs were treated with IGF2 or IGF2 + 3-MA. Cell proliferation was examined by CCK-8 kit after 48 h. (H and I) NFs were treated with IGF2 or IGF2+3-MA. NFs migration was detected by trans-well assay after 24 h (scale bar, 100 μm). (J) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. The AVOs formation was examined by AO staining (scale bar, 20 μm). (K) NFs were treated with CM, IGF2, and CM + IGF2 Ab. Protein expressions were detected by western blotting. (L) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. Cell proliferation was examined by CCK-8 kit after 48 h. (M and N) NFs were treated with IGF2, CM, CM + IGF2 Ab, and CM + 3-MA. NFs migration was detected by trans-well assay after 24 h (scale bar, 100 μm). (O and P) NFs were treated with RAPA (100 nM); α-SMA and FAP expressions were detected by western blotting (scale bar, 20 μm). (Q and R) NFs were treated with RAPA; NFs migration was detected by trans-well assay after 24 h. Ab, neutralizing antibody (scale bar, 100 μm). Data represents the mean ± SD from three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 .

    Article Snippet: Recombinant human IGF2 , Sino Biological , Cat#13032-HNAY.

    Techniques: Activation Assay, Staining, Fluorescence, Microscopy, Expressing, Western Blot, CCK-8 Assay, Migration

    Journal: iScience

    Article Title: Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

    doi: 10.1016/j.isci.2024.111269

    Figure Lengend Snippet:

    Article Snippet: Recombinant human IGF2 , Sino Biological , Cat#13032-HNAY.

    Techniques: Recombinant, Enzyme-linked Immunosorbent Assay

    PCR primer sequences

    Journal: iScience

    Article Title: Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

    doi: 10.1016/j.isci.2024.111269

    Figure Lengend Snippet: PCR primer sequences

    Article Snippet: Recombinant human IGF2 , Sino Biological , Cat#13032-HNAY.

    Techniques:

    FGR induces hippocampal Igf2 downregulation by DNA hypomethylation, and neuronal Igf2 deletion impairs synaptic plasticity. (A) qPCR analysis of Igf family mRNA levels in the hippocampi from 8‐week‐old NS and FGR mice. n = 6 mice in each group. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein levels in the hippocampi at Postnatal Day 1, 1, 4, 8 weeks from NS and FGR mice. n = 3 mice in each group. (D) Bisulfite methylation sequencing of ICR in the hippocampi from 8‐week‐old NS and FGR mice. n = 9 mice in each group. (E, F) qPCR analysis of H19 (E) and Dnmt1 (F) mRNA levels in the hippocampi of 8‐week‐old NS and FGR mice. n = 6 mice in each group. (G) WB analysis of IGF2 protein level in the hippocampi of Ctrl and IKO mice. n = 4 mice in each group. (H) LTP measurements were performed in the CA1 region of acute slices from Ctrl and IKO mice. n = 3 in each group. (I) Representative Golgi staining images of the hippocampal DG neurons from Ctrl and IKO mice. Scale bar, 100 μm. (J and K) Quantification of the dendritic branches (J) and total dendritic length (K) of the hippocampal DG neurons. n = 6 mice in each group, 4–5 neurons in each mouse. (L) Representative Golgi staining images of hippocampal DG neuronal dendritic spines. Scale bar, 5 μm. (M) Quantification of the dendritic spine density. n = 6 mice in each group, 4–5 spine pictures in each mouse. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (H) or unpaired Student's t ‐test (A, C–F, H, J, K, M). ** p < 0.01 and *** p < 0.001. See also Figures and .

    Journal: The FASEB Journal

    Article Title: Insulin‐Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice

    doi: 10.1096/fj.202402934R

    Figure Lengend Snippet: FGR induces hippocampal Igf2 downregulation by DNA hypomethylation, and neuronal Igf2 deletion impairs synaptic plasticity. (A) qPCR analysis of Igf family mRNA levels in the hippocampi from 8‐week‐old NS and FGR mice. n = 6 mice in each group. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein levels in the hippocampi at Postnatal Day 1, 1, 4, 8 weeks from NS and FGR mice. n = 3 mice in each group. (D) Bisulfite methylation sequencing of ICR in the hippocampi from 8‐week‐old NS and FGR mice. n = 9 mice in each group. (E, F) qPCR analysis of H19 (E) and Dnmt1 (F) mRNA levels in the hippocampi of 8‐week‐old NS and FGR mice. n = 6 mice in each group. (G) WB analysis of IGF2 protein level in the hippocampi of Ctrl and IKO mice. n = 4 mice in each group. (H) LTP measurements were performed in the CA1 region of acute slices from Ctrl and IKO mice. n = 3 in each group. (I) Representative Golgi staining images of the hippocampal DG neurons from Ctrl and IKO mice. Scale bar, 100 μm. (J and K) Quantification of the dendritic branches (J) and total dendritic length (K) of the hippocampal DG neurons. n = 6 mice in each group, 4–5 neurons in each mouse. (L) Representative Golgi staining images of hippocampal DG neuronal dendritic spines. Scale bar, 5 μm. (M) Quantification of the dendritic spine density. n = 6 mice in each group, 4–5 spine pictures in each mouse. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (H) or unpaired Student's t ‐test (A, C–F, H, J, K, M). ** p < 0.01 and *** p < 0.001. See also Figures and .

    Article Snippet: Igf2 recombination protein (CF61, 50 ng/mL, Novoprotein, China) was administered to the medium on Day 3, 9, or 12.

    Techniques: Methylation, Sequencing, Staining

    Increasing Igf2 rescues dendritic, synaptic, and memory impairments in cultured FGR hippocampal neurons and FGR mice. (A, B) Representative fluorescence images (A) and Sholl analysis of dendritic morphology (B) of cultured mouse hippocampal neurons from NS and FGR mice added with IGF2 protein or solvent control (Ctrl). Scale bar, 100 μm. n = 3 mice in each group, 8–10 neurons in each experiment. (C–E) Representative fluorescence images of synaptic sites (C), quantification of the percentage of intact synaptic contacts (D), and the total spine density (E) in primary hippocampal neurons of four groups. Scale bar, 20 μm. n = 3 in each group, 7–10 spine pictures in each experiment. (F) Representative Golgi staining images of the hippocampal DG neurons from NS and FGR mice injected with AAV‐Igf2 virus or its control. Scale bar, 50 μm. (G and H) Quantification of the dendritic branches (G) and total dendritic length (H) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–7 neurons in each mouse. (I and J) Representative Golgi staining of dendritic spines (I) and dendritic spine density (J) in four groups. Scale bar, 20 μm. n = 9 mice in each group, 9–10 spine pictures in each mouse. (K–N) MWM performance in four groups. (NS Ctrl: n = 12, NS Igf2: n = 11, FGR Ctrl: n = 12, FGR Igf2: n = 10). (K) Escape latency. (L) Time spent in each quadrant. The number of platform crossings was recorded 24 h (M) and 3 weeks (N) after the final training session. (O and P) Discrimination index (O) and object preferences (P) of the NOR test. (NS Ctrl: n = 13, NS Igf2: n = 11, FGR Ctrl: n = 13, FGR Igf2: n = 13). (Q and R) Freezing behavior in the 24 h (Q) and 7 days (R) fear recall test of the CFC test. n = 10 mice in each group. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (B, K, L and P), or one‐way ANOVA with Tukey's multiple comparisons test (D, E, G, H, J, M–O, Q, R). * p < 0.05, ** p < 0.01, and *** p < 0.001. See also Figure .

    Journal: The FASEB Journal

    Article Title: Insulin‐Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice

    doi: 10.1096/fj.202402934R

    Figure Lengend Snippet: Increasing Igf2 rescues dendritic, synaptic, and memory impairments in cultured FGR hippocampal neurons and FGR mice. (A, B) Representative fluorescence images (A) and Sholl analysis of dendritic morphology (B) of cultured mouse hippocampal neurons from NS and FGR mice added with IGF2 protein or solvent control (Ctrl). Scale bar, 100 μm. n = 3 mice in each group, 8–10 neurons in each experiment. (C–E) Representative fluorescence images of synaptic sites (C), quantification of the percentage of intact synaptic contacts (D), and the total spine density (E) in primary hippocampal neurons of four groups. Scale bar, 20 μm. n = 3 in each group, 7–10 spine pictures in each experiment. (F) Representative Golgi staining images of the hippocampal DG neurons from NS and FGR mice injected with AAV‐Igf2 virus or its control. Scale bar, 50 μm. (G and H) Quantification of the dendritic branches (G) and total dendritic length (H) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–7 neurons in each mouse. (I and J) Representative Golgi staining of dendritic spines (I) and dendritic spine density (J) in four groups. Scale bar, 20 μm. n = 9 mice in each group, 9–10 spine pictures in each mouse. (K–N) MWM performance in four groups. (NS Ctrl: n = 12, NS Igf2: n = 11, FGR Ctrl: n = 12, FGR Igf2: n = 10). (K) Escape latency. (L) Time spent in each quadrant. The number of platform crossings was recorded 24 h (M) and 3 weeks (N) after the final training session. (O and P) Discrimination index (O) and object preferences (P) of the NOR test. (NS Ctrl: n = 13, NS Igf2: n = 11, FGR Ctrl: n = 13, FGR Igf2: n = 13). (Q and R) Freezing behavior in the 24 h (Q) and 7 days (R) fear recall test of the CFC test. n = 10 mice in each group. The data are shown as mean ± SEM. Two‐way ANOVA with Sidak's multiple comparisons test (B, K, L and P), or one‐way ANOVA with Tukey's multiple comparisons test (D, E, G, H, J, M–O, Q, R). * p < 0.05, ** p < 0.01, and *** p < 0.001. See also Figure .

    Article Snippet: Igf2 recombination protein (CF61, 50 ng/mL, Novoprotein, China) was administered to the medium on Day 3, 9, or 12.

    Techniques: Cell Culture, Fluorescence, Solvent, Control, Staining, Injection, Virus

    Running exercise elevates hippocampal Igf2 expression and ameliorates cognitive defects in FGR mice. (A) qPCR analysis of Igf2 and Igf1 expression levels in the hippocampus of NS and FGR mice at 24 h after sedentary (Sed) or exercised (Run) treatment. n = 3 in each group. (B and C) qPCR analysis of Igf2, Igf1(B) and Dnmt1 (C) expression levels in the hippocampus of NS and FGR mice at 2 months after exercise training. n = 6 in each group. (D) Bisulfate methylation sequencing analysis of CTS1 in mouse hippocampi at 2 months after exercise training. n = 9 mice in each group. (E) Representative Golgi staining images of the hippocampal DG neurons from NS and FGR mice after sedentary (Sed) or exercised (Run) treatment. Scale bar, 50 μm. (F and G) Quantification of the dendritic branches (F) and total dendritic length (G) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–6 neurons in each mouse. (H and I) Representative Golgi staining dendritic spines (H) and dendritic spine density (I) in four groups. Scale bar, 20 μm. n = 9 mice in each group, 9–11 spine pictures in each mouse. (J–M) MWM performance in four groups. (NS Sed: n = 12, NS Run: n = 15, FGR Sed: n = 14, FGR Run: n = 12). (J) Escape latency. (K) Time spent in each quadrant. The number of platform crossings was recorded 24 h (L) and 3 weeks (M) after the final training session. (N and O) Discrimination index (N) and object preferences (O) of the NOR test. (NS Sed: n = 11, NS Run: n = 12, FGR Sed: n = 12, FGR Run: n = 12). (P and Q) Freezing behavior in the 24 h (P) and 7 days (Q) fear recall test of the CFC test (NS Sed: n = 14, NS Run: n = 11, FGR Sed: n = 13, FGR Run: n = 10). The data are shown as mean ± SEM. One‐way ANOVA with Tukey's multiple comparisons test (A–D, F, G, I, L–N, P, Q), or two‐way ANOVA with Sidak's multiple comparisons test (J, K, O) * p < 0.05, ** p < 0.01, and *** p < 0.001. See also Figure .

    Journal: The FASEB Journal

    Article Title: Insulin‐Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice

    doi: 10.1096/fj.202402934R

    Figure Lengend Snippet: Running exercise elevates hippocampal Igf2 expression and ameliorates cognitive defects in FGR mice. (A) qPCR analysis of Igf2 and Igf1 expression levels in the hippocampus of NS and FGR mice at 24 h after sedentary (Sed) or exercised (Run) treatment. n = 3 in each group. (B and C) qPCR analysis of Igf2, Igf1(B) and Dnmt1 (C) expression levels in the hippocampus of NS and FGR mice at 2 months after exercise training. n = 6 in each group. (D) Bisulfate methylation sequencing analysis of CTS1 in mouse hippocampi at 2 months after exercise training. n = 9 mice in each group. (E) Representative Golgi staining images of the hippocampal DG neurons from NS and FGR mice after sedentary (Sed) or exercised (Run) treatment. Scale bar, 50 μm. (F and G) Quantification of the dendritic branches (F) and total dendritic length (G) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–6 neurons in each mouse. (H and I) Representative Golgi staining dendritic spines (H) and dendritic spine density (I) in four groups. Scale bar, 20 μm. n = 9 mice in each group, 9–11 spine pictures in each mouse. (J–M) MWM performance in four groups. (NS Sed: n = 12, NS Run: n = 15, FGR Sed: n = 14, FGR Run: n = 12). (J) Escape latency. (K) Time spent in each quadrant. The number of platform crossings was recorded 24 h (L) and 3 weeks (M) after the final training session. (N and O) Discrimination index (N) and object preferences (O) of the NOR test. (NS Sed: n = 11, NS Run: n = 12, FGR Sed: n = 12, FGR Run: n = 12). (P and Q) Freezing behavior in the 24 h (P) and 7 days (Q) fear recall test of the CFC test (NS Sed: n = 14, NS Run: n = 11, FGR Sed: n = 13, FGR Run: n = 10). The data are shown as mean ± SEM. One‐way ANOVA with Tukey's multiple comparisons test (A–D, F, G, I, L–N, P, Q), or two‐way ANOVA with Sidak's multiple comparisons test (J, K, O) * p < 0.05, ** p < 0.01, and *** p < 0.001. See also Figure .

    Article Snippet: Igf2 recombination protein (CF61, 50 ng/mL, Novoprotein, China) was administered to the medium on Day 3, 9, or 12.

    Techniques: Expressing, Methylation, Sequencing, Staining

    Running exercise rescues impaired cognition in FGR mice via hippocampal Igf2. (A) Schematics of AAV9 construct knockdown of Igf2 expression and flow diagram of mouse experiments. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein level in the hippocampal DGs of mice injected with AAV‐shIgf2 virus and its control. n = 3 in each group. (D) Representative Golgi staining images of the hippocampal DG neurons from FGR mice injected with control virus after sedentary treatment (FGR‐Ctrl‐Sed) or exercised treatment (FGR‐Ctrl‐Run), or injected with AAV‐shIgf2 virus after sedentary treatment (FGR‐shIgf2‐Sed) or exercised treatment (FGR‐shIgf2‐Run). Scale bar, 100 μm. (E and F) Quantification of the dendritic branches (E) and total dendritic length (F) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–5 neurons in each mouse. (G and H) Representative Golgi staining dendritic spines (G) and dendritic spine density (H) in four groups. Scale bar, 5 μm. n = 6 mice in each group, 5 spine pictures in each mouse. (I–L) MWM performance in four groups. n = 8 mice in each group. (I) Escape latency. (J) Time spent in each quadrant. The number of platform crossings was recorded at 24 h (K) and 3 weeks (L) after the final training session. (M and N) Discrimination index (M) and object preferences (N) of the NOR test. n = 8 mice in each group. (O and P) Freezing behavior in the 24 h (O) and 7 days (P) fear recall test of the CFC test. n = 8 mice in each group. The data are shown as mean ± SEM. One‐way ANOVA with Tukey's multiple comparations test (E, F, H, K–M, O and P), two‐way ANOVA with Sidak's multiple comparisons test (I, J and N) or unpaired Student's t ‐test (C). * p < 0.05, ** p < 0.01, and *** p < 0.001.

    Journal: The FASEB Journal

    Article Title: Insulin‐Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice

    doi: 10.1096/fj.202402934R

    Figure Lengend Snippet: Running exercise rescues impaired cognition in FGR mice via hippocampal Igf2. (A) Schematics of AAV9 construct knockdown of Igf2 expression and flow diagram of mouse experiments. (B, C) WB representative picture (B) and analysis (C) of IGF2 protein level in the hippocampal DGs of mice injected with AAV‐shIgf2 virus and its control. n = 3 in each group. (D) Representative Golgi staining images of the hippocampal DG neurons from FGR mice injected with control virus after sedentary treatment (FGR‐Ctrl‐Sed) or exercised treatment (FGR‐Ctrl‐Run), or injected with AAV‐shIgf2 virus after sedentary treatment (FGR‐shIgf2‐Sed) or exercised treatment (FGR‐shIgf2‐Run). Scale bar, 100 μm. (E and F) Quantification of the dendritic branches (E) and total dendritic length (F) of the hippocampal DG neurons in four groups. n = 6 mice in each group, 4–5 neurons in each mouse. (G and H) Representative Golgi staining dendritic spines (G) and dendritic spine density (H) in four groups. Scale bar, 5 μm. n = 6 mice in each group, 5 spine pictures in each mouse. (I–L) MWM performance in four groups. n = 8 mice in each group. (I) Escape latency. (J) Time spent in each quadrant. The number of platform crossings was recorded at 24 h (K) and 3 weeks (L) after the final training session. (M and N) Discrimination index (M) and object preferences (N) of the NOR test. n = 8 mice in each group. (O and P) Freezing behavior in the 24 h (O) and 7 days (P) fear recall test of the CFC test. n = 8 mice in each group. The data are shown as mean ± SEM. One‐way ANOVA with Tukey's multiple comparations test (E, F, H, K–M, O and P), two‐way ANOVA with Sidak's multiple comparisons test (I, J and N) or unpaired Student's t ‐test (C). * p < 0.05, ** p < 0.01, and *** p < 0.001.

    Article Snippet: Igf2 recombination protein (CF61, 50 ng/mL, Novoprotein, China) was administered to the medium on Day 3, 9, or 12.

    Techniques: Construct, Knockdown, Expressing, Injection, Virus, Control, Staining

    Diagram demonstrating the potential link between IGF2 and spermatogenesis dysfunction. Blue arrows represent a decrease, red arrows represent an increase, solid arrows represent an effect on downstream factors, t-shaped arrows represent an inhibitory effect. IGF2, insulin-like growth factor 2; TNFα, tumor necrosis factor α; LPS, lipopolysaccharides; IL-6, interleukin-6; ROS, reactive oxygen species; ER, endoplasmic reticulum; T2DM, type II diabetes mellitus; IR, insulin resistance; GCs, germ cells.

    Journal: Molecular Medicine Reports

    Article Title: Insulin‑like growth factor 2 in spermatogenesis dysfunction (Review)

    doi: 10.3892/mmr.2025.13494

    Figure Lengend Snippet: Diagram demonstrating the potential link between IGF2 and spermatogenesis dysfunction. Blue arrows represent a decrease, red arrows represent an increase, solid arrows represent an effect on downstream factors, t-shaped arrows represent an inhibitory effect. IGF2, insulin-like growth factor 2; TNFα, tumor necrosis factor α; LPS, lipopolysaccharides; IL-6, interleukin-6; ROS, reactive oxygen species; ER, endoplasmic reticulum; T2DM, type II diabetes mellitus; IR, insulin resistance; GCs, germ cells.

    Article Snippet: Furthermore, Alfares et al ( ) show that IGF2 functions as a differential modulator of fat accumulation, favoring less visceral fat deposition and regulating preadipocyte differentiation and metabolism.

    Techniques:

    The insulin signaling pathway and cholesterol metabolism pathway in malignant hepatoblast‐like cells. A,B) Developmental trajectory of hepatocyte cells inferred by monocle2, colored by cell subtypes (A) and CNV levels (B). C) Representative signaling pathways during the developmental trajectory of hepatocyte cells inferred by monocle2. Heatmap showing the dynamic changes in gene expression along the pseudotime trajectory in branch 1 and branch 2. D) Gene set enrichment analysis (GSEA) of malignant HB‐like cells versus all hepatocyte cells in the indicated gene sets. ES, enrichment score; RM, ranked metric; NES, normalized enrichment score; FDR, false discovery rate. E. Heatmap of key gene expression related to the regulation of cholesterol metabolic process (GO: 0090181) and cellular response to insulin stimulus (GO: 0032869) in the three hepatocyte cell types. F) Violin plots showing INS, IGF1, IGF2, INSR, and IGF1R expression levels in the three hepatocyte cell populations. G) Representative IHC images of IGF2 staining of tissue sections. H) The expression levels of key proteins for the insulin signaling and cholesterol metabolic pathways in five pairs of hepatoblastoma and paracancerous tissues. I) Cholesterol concentrations were analyzed in primary hepatoblastoma tumors and paired paracancerous normal liver tissues. J) Lipid droplets (LDs) in primary hepatoblastoma tumors and paired paracancerous liver tissues were stained with BODIPY 493/503. K) BODIPY 493/503 and DUSP9 antibody co‐staining in primary hepatoblastoma tumors.

    Journal: Advanced Science

    Article Title: Malignant Hepatoblast‐Like Cells Sustain Stemness via IGF2‐Dependent Cholesterol Accumulation in Hepatoblastoma

    doi: 10.1002/advs.202407671

    Figure Lengend Snippet: The insulin signaling pathway and cholesterol metabolism pathway in malignant hepatoblast‐like cells. A,B) Developmental trajectory of hepatocyte cells inferred by monocle2, colored by cell subtypes (A) and CNV levels (B). C) Representative signaling pathways during the developmental trajectory of hepatocyte cells inferred by monocle2. Heatmap showing the dynamic changes in gene expression along the pseudotime trajectory in branch 1 and branch 2. D) Gene set enrichment analysis (GSEA) of malignant HB‐like cells versus all hepatocyte cells in the indicated gene sets. ES, enrichment score; RM, ranked metric; NES, normalized enrichment score; FDR, false discovery rate. E. Heatmap of key gene expression related to the regulation of cholesterol metabolic process (GO: 0090181) and cellular response to insulin stimulus (GO: 0032869) in the three hepatocyte cell types. F) Violin plots showing INS, IGF1, IGF2, INSR, and IGF1R expression levels in the three hepatocyte cell populations. G) Representative IHC images of IGF2 staining of tissue sections. H) The expression levels of key proteins for the insulin signaling and cholesterol metabolic pathways in five pairs of hepatoblastoma and paracancerous tissues. I) Cholesterol concentrations were analyzed in primary hepatoblastoma tumors and paired paracancerous normal liver tissues. J) Lipid droplets (LDs) in primary hepatoblastoma tumors and paired paracancerous liver tissues were stained with BODIPY 493/503. K) BODIPY 493/503 and DUSP9 antibody co‐staining in primary hepatoblastoma tumors.

    Article Snippet: The IGF2 protein in the collected human serums were confirmed with enzyme‐linked immunosorbent assay (Cusabio, IGF2 human ELISA kit).

    Techniques: Protein-Protein interactions, Gene Expression, Expressing, Staining

    IGF2 sustains hepatoblastoma stemness via abnormal cholesterol accumulation. A) Effects of IGF2 on the tumorsphere formation of HepG2 cells. Scale bar, 50 µm. Means ± SD are shown ( n = 3). B) The expression level of IGF2‐activated signaling pathway‐related proteins in HepG2 cells treated with IGF2 for five days was analyzed by western blots. C) The expression levels of HB stemness‐related proteins in HepG2 cells treated with IGF2 for five days were analyzed by western blots. D) Pearson's correlation analysis shows the correlation between response to insulin‐like growth factor stimulus (GO: 1990418) and the regulation of cholesterol metabolic process (GO: 0090181) in hepatoblastoma and normal tissue pairs using scRNA sequencing ( n = 14). E) The expression levels of cholesterol metabolic pathway‐related proteins in HepG2 cells treated with IGF2 were analyzed by western blots. F) Cholesterol concentrations were analyzed in HepG2 cells treated with IGF2 for 5 days. G) Lipid droplets (LDs) in HepG2 cells treated with IGF2 for 5 days were stained with BODIPY 493/503. Scale bar, 50 µm. H) Representative images of organoids treated with cholesterol at 0, 10, and 25 µ m on day 5 are shown. Scale bar, 50 µm. I) The expression of HB stemness‐related genes in hepatoblastoma PDOs with or without cholesterol treatment was analyzed by qRT‐PCR. Means ± SD ( n = 3) are shown. J) HepG2‐control cells/HepG2‐IGF2 KD cells were subcutaneously injected into nude mice. Tumor volume changes were examined, and the mice were euthanized 40 days after tumor cell injection. K) The expression levels of IGF2, SREBF2, DUSP9, and LDs in mice tumors were detected by IHC analysis. * p < 0.05, ** p < 0.01, *** p < 0.001 by the Student's t ‐test. L) Cholesterol concentrations were measured in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ). M) LDs in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ) treatment were stained with BODIPY 493/503. Scale bar, 50 µm. N) Tumorsphere formation assay comparing the effect of IGF2 (100 µ m ) and MBCD (1 m m ) treatments on HepG2 cells. Means ± SD are shown ( n = 3). Scale bar, 50 µm. O) The expression of HB stemness‐related proteins in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ) was analyzed by western blots.

    Journal: Advanced Science

    Article Title: Malignant Hepatoblast‐Like Cells Sustain Stemness via IGF2‐Dependent Cholesterol Accumulation in Hepatoblastoma

    doi: 10.1002/advs.202407671

    Figure Lengend Snippet: IGF2 sustains hepatoblastoma stemness via abnormal cholesterol accumulation. A) Effects of IGF2 on the tumorsphere formation of HepG2 cells. Scale bar, 50 µm. Means ± SD are shown ( n = 3). B) The expression level of IGF2‐activated signaling pathway‐related proteins in HepG2 cells treated with IGF2 for five days was analyzed by western blots. C) The expression levels of HB stemness‐related proteins in HepG2 cells treated with IGF2 for five days were analyzed by western blots. D) Pearson's correlation analysis shows the correlation between response to insulin‐like growth factor stimulus (GO: 1990418) and the regulation of cholesterol metabolic process (GO: 0090181) in hepatoblastoma and normal tissue pairs using scRNA sequencing ( n = 14). E) The expression levels of cholesterol metabolic pathway‐related proteins in HepG2 cells treated with IGF2 were analyzed by western blots. F) Cholesterol concentrations were analyzed in HepG2 cells treated with IGF2 for 5 days. G) Lipid droplets (LDs) in HepG2 cells treated with IGF2 for 5 days were stained with BODIPY 493/503. Scale bar, 50 µm. H) Representative images of organoids treated with cholesterol at 0, 10, and 25 µ m on day 5 are shown. Scale bar, 50 µm. I) The expression of HB stemness‐related genes in hepatoblastoma PDOs with or without cholesterol treatment was analyzed by qRT‐PCR. Means ± SD ( n = 3) are shown. J) HepG2‐control cells/HepG2‐IGF2 KD cells were subcutaneously injected into nude mice. Tumor volume changes were examined, and the mice were euthanized 40 days after tumor cell injection. K) The expression levels of IGF2, SREBF2, DUSP9, and LDs in mice tumors were detected by IHC analysis. * p < 0.05, ** p < 0.01, *** p < 0.001 by the Student's t ‐test. L) Cholesterol concentrations were measured in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ). M) LDs in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ) treatment were stained with BODIPY 493/503. Scale bar, 50 µm. N) Tumorsphere formation assay comparing the effect of IGF2 (100 µ m ) and MBCD (1 m m ) treatments on HepG2 cells. Means ± SD are shown ( n = 3). Scale bar, 50 µm. O) The expression of HB stemness‐related proteins in HepG2 cells treated with IGF2 (100 µ m ) and MBCD (1 m m ) was analyzed by western blots.

    Article Snippet: The IGF2 protein in the collected human serums were confirmed with enzyme‐linked immunosorbent assay (Cusabio, IGF2 human ELISA kit).

    Techniques: Expressing, Western Blot, Sequencing, Staining, Quantitative RT-PCR, Control, Injection, Paraffin-embedded Immunohistochemistry, Tube Formation Assay

    SREBF2 mediates abnormal cholesterol accumulation in the activated IGF2 signaling pathway. A) Regulon activity scores of three hepatocyte cell types were calculated using SCENIC. B) GO enrichment analysis for SREBF2 target genes calculated using SCENIC. C) Cholesterol concentrations were analyzed in HepG2 cells with SREBF2 expression. D) LDs were stained with BODIPY 493/503 in HepG2 cells with SREBF2 overexpression. Scale bar, 50 µm. E) Tumorsphere formation assay comparing the effect of SREBF2 on HepG2 cells. Means ± SD are shown ( n = 3). F) The expression of HB stemness‐related proteins was analyzed in HepG2 cells with SREBF2 overexpression using RT‐PCR. G) Schematic diagram of HCD and Fatostain combined treatment. Mice were injected with HepG2 tumor cells subcutaneously after 14 days of HCD feeding. Ten days later, the tumor‐bearing mice were treated with Fatostain at 15 mg kg −1 daily. H) Tumor volume changes were examined, and the mice were euthanized 52 days after treatment. I) Mice were euthanized, and the cholesterol concentrations were measured in tumor tissues. Data represent the mean ± SD of five samples in each group per time point. J) The expression levels of SREBF2, DUSP9, and LDs in mice tumors were analyzed using IHC staining. * p < 0.05, ** p < 0.01, *** p < 0.001 by the Student's t ‐test. K) Cholesterol concentrations were analyzed in HepG2 cells treated with IGF2 and SREBF2 siRNA. L) LDs in HepG2 cells with the indicated treatments were stained with BODIPY 493/503. Scale bar, 50 µm. M) Tumorsphere formation assay comparing the effect of the indicated treatments on HepG2 cells. Means ± SD are shown ( n = 3). N) The expression of HB stemness‐related proteins in HepG2 cells with the indicated treatments was analyzed by western blots.

    Journal: Advanced Science

    Article Title: Malignant Hepatoblast‐Like Cells Sustain Stemness via IGF2‐Dependent Cholesterol Accumulation in Hepatoblastoma

    doi: 10.1002/advs.202407671

    Figure Lengend Snippet: SREBF2 mediates abnormal cholesterol accumulation in the activated IGF2 signaling pathway. A) Regulon activity scores of three hepatocyte cell types were calculated using SCENIC. B) GO enrichment analysis for SREBF2 target genes calculated using SCENIC. C) Cholesterol concentrations were analyzed in HepG2 cells with SREBF2 expression. D) LDs were stained with BODIPY 493/503 in HepG2 cells with SREBF2 overexpression. Scale bar, 50 µm. E) Tumorsphere formation assay comparing the effect of SREBF2 on HepG2 cells. Means ± SD are shown ( n = 3). F) The expression of HB stemness‐related proteins was analyzed in HepG2 cells with SREBF2 overexpression using RT‐PCR. G) Schematic diagram of HCD and Fatostain combined treatment. Mice were injected with HepG2 tumor cells subcutaneously after 14 days of HCD feeding. Ten days later, the tumor‐bearing mice were treated with Fatostain at 15 mg kg −1 daily. H) Tumor volume changes were examined, and the mice were euthanized 52 days after treatment. I) Mice were euthanized, and the cholesterol concentrations were measured in tumor tissues. Data represent the mean ± SD of five samples in each group per time point. J) The expression levels of SREBF2, DUSP9, and LDs in mice tumors were analyzed using IHC staining. * p < 0.05, ** p < 0.01, *** p < 0.001 by the Student's t ‐test. K) Cholesterol concentrations were analyzed in HepG2 cells treated with IGF2 and SREBF2 siRNA. L) LDs in HepG2 cells with the indicated treatments were stained with BODIPY 493/503. Scale bar, 50 µm. M) Tumorsphere formation assay comparing the effect of the indicated treatments on HepG2 cells. Means ± SD are shown ( n = 3). N) The expression of HB stemness‐related proteins in HepG2 cells with the indicated treatments was analyzed by western blots.

    Article Snippet: The IGF2 protein in the collected human serums were confirmed with enzyme‐linked immunosorbent assay (Cusabio, IGF2 human ELISA kit).

    Techniques: Activity Assay, Expressing, Staining, Over Expression, Tube Formation Assay, Reverse Transcription Polymerase Chain Reaction, Injection, Immunohistochemistry, Western Blot

    Serum IGF2 is a potential diagnostic biomarker for hepatoblastoma patients. A) The column scatter plot shows IGF2 concentrations in serum in the hepatoblastoma group and the control group of children. B) The ROC curve for using serum IGF2 as a diagnostic biomarker. C) The column scatter plot shows serum IGF2 concentration in the PRETEXTI‐II hepatoblastoma group and the PRETEXT III‐IV hepatoblastoma group. D) The column scatter plot shows serum IGF2 concentrations in the before‐treatment hepatoblastoma group and the after‐treatment hepatoblastoma group. E) The column scatter plot shows serum AFP concentrations in the hepatoblastoma group and the control group of children. F) The ROC curve for using serum AFP levels as a diagnostic biomarker. G) The column scatter plot showed serum AFP concentrations in the PRETEXTI‐II hepatoblastoma group and the PRETEXT III‐IV hepatoblastoma group. H) The column scatter plot shows serum AFP concentrations in the before‐treatment hepatoblastoma group and the after‐treatment hepatoblastoma group. p < 0.05, ** p < 0.01, *** p < 0.001.

    Journal: Advanced Science

    Article Title: Malignant Hepatoblast‐Like Cells Sustain Stemness via IGF2‐Dependent Cholesterol Accumulation in Hepatoblastoma

    doi: 10.1002/advs.202407671

    Figure Lengend Snippet: Serum IGF2 is a potential diagnostic biomarker for hepatoblastoma patients. A) The column scatter plot shows IGF2 concentrations in serum in the hepatoblastoma group and the control group of children. B) The ROC curve for using serum IGF2 as a diagnostic biomarker. C) The column scatter plot shows serum IGF2 concentration in the PRETEXTI‐II hepatoblastoma group and the PRETEXT III‐IV hepatoblastoma group. D) The column scatter plot shows serum IGF2 concentrations in the before‐treatment hepatoblastoma group and the after‐treatment hepatoblastoma group. E) The column scatter plot shows serum AFP concentrations in the hepatoblastoma group and the control group of children. F) The ROC curve for using serum AFP levels as a diagnostic biomarker. G) The column scatter plot showed serum AFP concentrations in the PRETEXTI‐II hepatoblastoma group and the PRETEXT III‐IV hepatoblastoma group. H) The column scatter plot shows serum AFP concentrations in the before‐treatment hepatoblastoma group and the after‐treatment hepatoblastoma group. p < 0.05, ** p < 0.01, *** p < 0.001.

    Article Snippet: The IGF2 protein in the collected human serums were confirmed with enzyme‐linked immunosorbent assay (Cusabio, IGF2 human ELISA kit).

    Techniques: Diagnostic Assay, Biomarker Discovery, Control, Concentration Assay

    Schematic diagram of malignant HB‐like cells demonstrating self‐sustaining ability via IGF2‐dependent mechanisms in hepatoblastoma.

    Journal: Advanced Science

    Article Title: Malignant Hepatoblast‐Like Cells Sustain Stemness via IGF2‐Dependent Cholesterol Accumulation in Hepatoblastoma

    doi: 10.1002/advs.202407671

    Figure Lengend Snippet: Schematic diagram of malignant HB‐like cells demonstrating self‐sustaining ability via IGF2‐dependent mechanisms in hepatoblastoma.

    Article Snippet: The IGF2 protein in the collected human serums were confirmed with enzyme‐linked immunosorbent assay (Cusabio, IGF2 human ELISA kit).

    Techniques:

    Effects of IGF2 knockdown in XF-iMSCs on Col6a1 -KO/NSG MuSC differentiation. a mRNA expression of IGF2 and PXDN . The mRNA expression level of each gene was analyzed using RT-qPCR in Ad-MSCs, BM-MSCs, and XF-iMSCs. Levels are shown relative to those in XF-iMSCs. Data are shown as the mean ± SD. b Concentration of IGF2 in the culture supernatants of Ad-MSCs, BM-MSCs, and XF-iMSCs as obtained using ELISA. Data are shown as the mean ± SD. c mRNA expression level and concentration of IGF2 in the culture on co-culture day 3. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after single culture or co-culture with XF-iMSC, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. e Total number of DAPI + /hLamin A/C- mouse myogenic cells 3 days after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. f Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations 3 days after co-culture. Data from three independent experiments are shown as the mean ± SD. g mRNA expression level and concentration of IGF2 in the culture on co-culture day 6. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. h Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after single culture or co-culture with XF-iMSCs, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. i, j Area of MHC + myotubes ( i ) and number of MHC + myotubes ( j ) with four or more nuclei on day 6 after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. co-cluture experiment: n = 6 (XF-iMSCs, XF-iMSC_ IGF2-KD and XF-iMSC_mock), n = 3 (single culture). qPCR and ELISA experiment: n = 2 (Ad-MSCs, BM-MSCs, XF-iMSCs)

    Journal: Stem Cell Research & Therapy

    Article Title: Distinct muscle regenerative capacity of human induced pluripotent stem cell-derived mesenchymal stromal cells in Ullrich congenital muscular dystrophy model mice

    doi: 10.1186/s13287-024-03951-6

    Figure Lengend Snippet: Effects of IGF2 knockdown in XF-iMSCs on Col6a1 -KO/NSG MuSC differentiation. a mRNA expression of IGF2 and PXDN . The mRNA expression level of each gene was analyzed using RT-qPCR in Ad-MSCs, BM-MSCs, and XF-iMSCs. Levels are shown relative to those in XF-iMSCs. Data are shown as the mean ± SD. b Concentration of IGF2 in the culture supernatants of Ad-MSCs, BM-MSCs, and XF-iMSCs as obtained using ELISA. Data are shown as the mean ± SD. c mRNA expression level and concentration of IGF2 in the culture on co-culture day 3. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after single culture or co-culture with XF-iMSC, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. e Total number of DAPI + /hLamin A/C- mouse myogenic cells 3 days after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. f Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations 3 days after co-culture. Data from three independent experiments are shown as the mean ± SD. g mRNA expression level and concentration of IGF2 in the culture on co-culture day 6. Data are presented as the mean ± SD. mRNA expression levels are shown with levels relative to those in XF-iMSCs. h Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after single culture or co-culture with XF-iMSCs, XF-iMSC_ IGF2 -KD, or XF-iMSC_mock. i, j Area of MHC + myotubes ( i ) and number of MHC + myotubes ( j ) with four or more nuclei on day 6 after co-culture. Data are expressed relative to XF-iMSCs and are presented as the mean ± SD of three independent experiments. co-cluture experiment: n = 6 (XF-iMSCs, XF-iMSC_ IGF2-KD and XF-iMSC_mock), n = 3 (single culture). qPCR and ELISA experiment: n = 2 (Ad-MSCs, BM-MSCs, XF-iMSCs)

    Article Snippet: Insulin growth factor 2 (IGF2) protein was quantified using a Human IGF-II/IGF2 Quantizing ELISA kit (DG200, R&D Systems, Minneapolis, MSP, USA).

    Techniques: Knockdown, Expressing, Quantitative RT-PCR, Concentration Assay, Enzyme-linked Immunosorbent Assay, Co-Culture Assay, Immunofluorescence, Derivative Assay

    Effects of IGF2 supplementation on Col6a1 -KO/NSG MuSC differentiation. a Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after IGF2 supplementation (IGF2-treated) or without IGF2 treatment (IGF2-untreated). b Total number of DAPI + /hLamin A/C- mouse myogenic cells after 3 days of culture. Data are expressed relative to IGF2-untreated and are presented as the mean ± SD of three independent experiments. c Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations after 3 days of culture. Data from three independent experiments are shown as the mean ± SD. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after IGF2 supplementation (IGF2-treated) or without IGF2 treatment (IGF2-untreated). e, f Area of MHC + myotubes ( e ) and number of MHC + myotubes with two or more nuclei ( f ) 6 days after co-culture. Data are expressed relative to IGF2-untreated and are presented as the mean ± SD of three independent experiments. * p < 0.05. n = 3 (IGF2 treated, IGF2 untreated)

    Journal: Stem Cell Research & Therapy

    Article Title: Distinct muscle regenerative capacity of human induced pluripotent stem cell-derived mesenchymal stromal cells in Ullrich congenital muscular dystrophy model mice

    doi: 10.1186/s13287-024-03951-6

    Figure Lengend Snippet: Effects of IGF2 supplementation on Col6a1 -KO/NSG MuSC differentiation. a Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 3 days after IGF2 supplementation (IGF2-treated) or without IGF2 treatment (IGF2-untreated). b Total number of DAPI + /hLamin A/C- mouse myogenic cells after 3 days of culture. Data are expressed relative to IGF2-untreated and are presented as the mean ± SD of three independent experiments. c Percentage of Pax7 + /MyoD-, Pax7 + /MyoD + , and Pax7-/MyoD + cell populations after 3 days of culture. Data from three independent experiments are shown as the mean ± SD. d Representative immunofluorescence images of Col6a1 -KO/NSG mouse-derived MuSCs 6 days after IGF2 supplementation (IGF2-treated) or without IGF2 treatment (IGF2-untreated). e, f Area of MHC + myotubes ( e ) and number of MHC + myotubes with two or more nuclei ( f ) 6 days after co-culture. Data are expressed relative to IGF2-untreated and are presented as the mean ± SD of three independent experiments. * p < 0.05. n = 3 (IGF2 treated, IGF2 untreated)

    Article Snippet: Insulin growth factor 2 (IGF2) protein was quantified using a Human IGF-II/IGF2 Quantizing ELISA kit (DG200, R&D Systems, Minneapolis, MSP, USA).

    Techniques: Immunofluorescence, Derivative Assay, Co-Culture Assay

    Hippocampal administration of recombinant IGF2 normalizes both memory consolidation and relative cfos expression in aged Tsc2 +/− mice. (a) Schematic overview of 7d NORT including IGF2 administration on day 2 within 2 h after second training phase. (b), 7d NORT approach of aged Tsc2 mutant mice 7 days after IGF2 injection showed a significant enhancement of memory consolidation measured as discrimination index compared to the PBS‐injected mutant mice (two tailed t test: P (baseline) = 5,89e‐9, n (WT) = 32, n ( Tsc2+/− ) = 34); p (PBS) = 0.0066, n (WT) = 13, n ( Tsc2 +/− ) = 11; p (IGF2) = 0.4433, n (WT) = 18, n ( Tsc2 +/− ) = 17. (c) Relative mRNA expression levels of cfos in the hippocampus of aged Tsc2 mutants after IGF2 administration compared to the control group. No significant difference in Tsc2 +/− mice compared to wildtype controls after IGF2 treatment (two‐tailed t test: p (PBS) = 0.0004, n (WT) = 4, n ( Tsc2 +/− ) = 7); p (IGF2) = 0.2329, n (WT) = 6, n ( Tsc2 +/− ) = 8. Values were normalized against Gapdh and are presented as mean ± SEM, * p < 0.05, *** p < 0.001. Quantification was performed using Excel.

    Journal: Aging Cell

    Article Title: Premature cognitive decline in a mouse model of tuberous sclerosis

    doi: 10.1111/acel.14318

    Figure Lengend Snippet: Hippocampal administration of recombinant IGF2 normalizes both memory consolidation and relative cfos expression in aged Tsc2 +/− mice. (a) Schematic overview of 7d NORT including IGF2 administration on day 2 within 2 h after second training phase. (b), 7d NORT approach of aged Tsc2 mutant mice 7 days after IGF2 injection showed a significant enhancement of memory consolidation measured as discrimination index compared to the PBS‐injected mutant mice (two tailed t test: P (baseline) = 5,89e‐9, n (WT) = 32, n ( Tsc2+/− ) = 34); p (PBS) = 0.0066, n (WT) = 13, n ( Tsc2 +/− ) = 11; p (IGF2) = 0.4433, n (WT) = 18, n ( Tsc2 +/− ) = 17. (c) Relative mRNA expression levels of cfos in the hippocampus of aged Tsc2 mutants after IGF2 administration compared to the control group. No significant difference in Tsc2 +/− mice compared to wildtype controls after IGF2 treatment (two‐tailed t test: p (PBS) = 0.0004, n (WT) = 4, n ( Tsc2 +/− ) = 7); p (IGF2) = 0.2329, n (WT) = 6, n ( Tsc2 +/− ) = 8. Values were normalized against Gapdh and are presented as mean ± SEM, * p < 0.05, *** p < 0.001. Quantification was performed using Excel.

    Article Snippet: A single dose of recombinant mouse IGF2 protein (R&D Systems, #792‐MG) was stereotactically injected into the hippocampus of 8–10 months old Tsc2 +/− mice and wildtype littermates after the training phase 2 (day 2) of the 7 days NORT (Figure ).

    Techniques: Recombinant, Expressing, Mutagenesis, Injection, Two Tailed Test, Control