Journal: Cell Death & Disease

Article Title: Generation of proliferative hESC-derived grape-clustered hepatocyte organoids with multipolar architecture as regenerative counterpart via synergy of YAP and IGF2 pathways

doi: 10.1038/s41419-026-08635-y

Figure Lengend Snippet: A KEGG pathway analysis of G-heporgs and S-heporgs. B Heatmap showing ligands and receptors in G-heporgs and S-heporgs. C Matched signaling of IGF2 and IGF1R using STRING database. D Expressions of IGF2 and IGF1R were analyzed by RT-qPCR in different organoids. n = 4 biologically independent experiments. E IGF2 secretion from culture medium at different days (day 1 was the first day that observed the generation of G-heporgs). n = 4 biologically independent experiments. F Immunostaining for IGF1R and Ki67. Nuclei were stained with DAPI. Scale bar = 25 μm. G Experimental strategy to evaluate the effect of exogenous IGF2 and LY294002 (PI3K-AKT inhibitor) on G-heporgs. H Representative morphologies of G-heporgs after the treatment with or without IGF2 and LY294002 at different days. Scale bar = 100 μm. I Quantification of the formation efficiency ( n = 4 biologically independent experiments) and diameter ( n = 40 organoids) of G-heporgs at day 14 after different treatments. J Immunostaining of ASGPR, HNF4α, ALB, Ecad and Ki67 for G-heporgs treated with IGF2. Nuclei were stained with DAPI. Scale bar = 50 μm. K Western blot assessment for the expression of p-AKT(Thr308), AKT, p-GSK3β(Ser9) and GSK3β in G-heporgs after different treatments. L Schematic illustration of cell-cell interactions between G-heporgs and S-heporgs. Results were presented as mean ± SD. Statistical significance was determined using one‑way ANOVA followed by Tukey post‑test. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: The concentrations of IGF2, IL32, and CCL20 were quantified using a Human IGF2 ELISA kit (Jingmei Biotechnology, JM-0862H2), a Human IL32 ELISA kit (SAB), and a Human CCL20 ELISA kit (Jingmei Biotechnology, JM-5919H2), respectively, according to the manufacturers’ instructions.

Techniques: Quantitative RT-PCR, Immunostaining, Staining, Western Blot, Expressing

Journal: Cell Death & Disease

Article Title: Generation of proliferative hESC-derived grape-clustered hepatocyte organoids with multipolar architecture as regenerative counterpart via synergy of YAP and IGF2 pathways

doi: 10.1038/s41419-026-08635-y

Figure Lengend Snippet: A Representative images of G-heporgs after the treatment with YAP agonist (GA017) or inhibitor (Verteporfin) in optimized heporg medium (OHM). B Relative cell number ( n = 4 biologically independent experiments) and organoid diameter ( n = 30 organoids) of G-heporgs at day 5 after the treatment. C Representative morphologies of G-heporgs after the treatment with GA017 at different days. Scale bar = 100 μm. D Immunostaining of Factin and YAP. Nuclei were stained with DAPI. Scale bar = 50 μm. Yellow arrows indicate YAP with nuclear localization, red arrows indicate YAP without nuclear localization. E The quantification of YAP nuclear localization. n = 4 biologically independent experiments. F H&E staining for G-heporgs treated with or without GA017, and the quantification of the percentage of cysts in organoids. Scale bar = 100 μm. n = 4 biologically independent experiments. G Heatmap of G-heporgs treated with or without GA017 for genes related to proliferation, mature and YAP. H GSEA analysis. I The relative fold increment of G-heporgs in the EM with GA017 or IGF2. Each dot represents a passage event. n = 4 biologically independent experiments. Results were presented as mean ± SD. Statistical significance was determined using two‑way repeated measures ANOVA followed by Tukey’s multiple comparisons test, one‑way ANOVA followed by Tukey post‑test and unpaired two-tailed Student’s t-test. *** p < 0.001.

Article Snippet: The concentrations of IGF2, IL32, and CCL20 were quantified using a Human IGF2 ELISA kit (Jingmei Biotechnology, JM-0862H2), a Human IL32 ELISA kit (SAB), and a Human CCL20 ELISA kit (Jingmei Biotechnology, JM-5919H2), respectively, according to the manufacturers’ instructions.

Techniques: Immunostaining, Staining, Two Tailed Test

Journal: Frontiers in Immunology

Article Title: PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance

doi: 10.3389/fimmu.2026.1790942

Figure Lengend Snippet: PTN regulates endometrial stromal cell decidualization through the IGF-2 signaling axis. (A) PPI network of PTN, IGF-2, IGFBP1, LIF, PRL, and other decidualization-related genes. (B) The expression levels of PTN and its interacting partners (IGF-2, WNT4, PRL, IGFBP1, and LIF) in the RIF (left) and RPL (right) datasets. (C) Expressions of decidualization-related genes (including IGFBP1 , LIF , PRL , and WNT4 ) in NC or si PTN hESCs after treatment with control vehicle, cAMP, and IGF-2 via RT-qPCR (n = 9). (D) Immunoblotting for PTN, IGFBP1, and PRL expression levels with control vehicle, cAMP, and IGF-2. (E) ELISA for IGF-2 levels with control vehicle, cAMP, and IGF-2. (F) Schematic diagram of the experiments performed using the different treatments of hESCs. Data are presented as mean ± SEM and analyzed using t-test or one-way ANOVA test. * compared with NC treated with control vehicle, # compared with si PTN treated with control vehicle, $ compared with si PTN treated with control cAMP (NS, no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ####p < 0.0001, $p < 0.05, $$p < 0.01, $$$p < 0.001, $$$$p< 0.0001). PPI, protein–protein interaction; RIF, recurrent implantation failure; RPL, recurrent pregnancy loss; hESCs, human endometrial stromal cells; cAMP, cyclic adenosine monophosphate.

Article Snippet: The remaining cells were digested with trypsin and inoculated into a new culture dish, and they were treated with control vehicle or IGF-2 (50 ng/mL, R&D Systems, Minneapolis, MN, USA, 292-G2) for 48 h and then collected for quantitative real-time polymerase chain reaction (qRT-PCR).

Techniques: Expressing, Control, Quantitative RT-PCR, Western Blot, Enzyme-linked Immunosorbent Assay

Journal: Frontiers in Immunology

Article Title: PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance

doi: 10.3389/fimmu.2026.1790942

Figure Lengend Snippet: IGF-2 promotes decidualization and rescues decidualization defects caused by PTN deficiency. (A) Schematic diagram of the experiments performed using the different treatments of ESCs isolated from endometrium of RIF and RPL patients. (B, C) RT-qPCR analysis of levels of decidualization-related genes in ESCs isolated from endometrium of RIF (B) and RPL (C) patients after IGF-2 (50 ng/mL) treatment for 48 h (n = 9). (D) The flowchart depicts the steps involved in establishing a mouse model of intrauterine perfusion with siRNA-mediated knockdown of PTN and then supplemented with IGF-2 (50 ng/mL) through tail vein injection. (E) Expression of PTN after Ptn knockdown and supplemented with control vehicle or IGF-2 (50 ng/mL) in the mouse endometrium, measured by immunofluorescence, and quantitative analysis of immunofluorescence was performed (n = 6). (F) RT-qPCR analysis of levels of decidualization-related genes after Ptn knockdown and supplemented with control vehicle or IGF-2 (50 ng/mL) in the mouse endometrium (n = 6). Data are presented as mean ± SEM and analyzed using t-test or one-way ANOVA test. * compared with NC treated with control vehicle, # compared with si PTN treated with control vehicle (NS, no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001, ****p< 0.0001, ## p < 0.01, ### p < 0.001, #### p < 0.0001). ESCs, endometrial stromal cells; PPI, protein–protein interaction; RIF, recurrent implantation failure.

Article Snippet: The remaining cells were digested with trypsin and inoculated into a new culture dish, and they were treated with control vehicle or IGF-2 (50 ng/mL, R&D Systems, Minneapolis, MN, USA, 292-G2) for 48 h and then collected for quantitative real-time polymerase chain reaction (qRT-PCR).

Techniques: Isolation, Quantitative RT-PCR, Knockdown, Injection, Expressing, Control, Immunofluorescence

Journal: Frontiers in Immunology

Article Title: PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance

doi: 10.3389/fimmu.2026.1790942

Figure Lengend Snippet: PTN deficiency induces endometrial immune imbalance and leads to adverse pregnancy outcomes, which can be partially reversed by IGF-2. (A) PPI network of PTN, IGF-2, CXCR4, CD4, CD8, CD56, and other immunoregulators. (B, C) Flow cytometry analysis (B) and statistical quantification (C) of cell populations of NK cells and T cells, and the expression levels of CD16, CXCR4, and GZMB in NK cell form the endometrial tissues of NC and si PTN mice treated with control vehicle or IGF-2 (50 ng/mL) (n = 6). (D) The flowchart depicts the steps involved in establishing a mouse model of intrauterine perfusion with siRNA-mediated knockdown of Ptn and then supplemented with IGF-2 (50 ng/mL) through tail vein injection for 2 days; then, these female mice were mated with fertile male mice; analysis of fertility, including pregnancy rate, IF, and fluorescence-activated cell sorting (FACS). were performed at gestational day 13.5. (E) Representative images of uteri from pregnant mice in the NC and si PTN mice treated with control vehicle or IGF-2 (50 ng/mL) at gestational day 13.5 (n = 6) (arrow shows the absorption site). (F) Pregnancy rate (%) in NC and si PTN mice treated with control vehicle or IGF-2 (50 ng/mL) (n = 15). (G) Quantification of embryo numbers (left) and absorption rate (right) per mouse in NC (n = 13) and si PTN mice treated with control vehicle (n = 6) or IGF-2 (50 ng/mL) (n = 11) at gestational day 13.5. Data are presented as mean ± SEM and analyzed using one-way ANOVA test or χ 2 test. * Compared with NC treated with control vehicle, # compared with si PTN treated with control vehicle (NS, no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ## p < 0.01, ### p < 0.001, #### p < 0.0001). IF, immunofluorescence.

Article Snippet: The remaining cells were digested with trypsin and inoculated into a new culture dish, and they were treated with control vehicle or IGF-2 (50 ng/mL, R&D Systems, Minneapolis, MN, USA, 292-G2) for 48 h and then collected for quantitative real-time polymerase chain reaction (qRT-PCR).

Techniques: Flow Cytometry, Expressing, Control, Knockdown, Injection, Fluorescence, FACS, Immunofluorescence