igf1  (R&D Systems)

Journal: Nature Communications

Article Title: Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development

doi: 10.1038/s41467-026-68675-y

Figure Lengend Snippet: a Differentiation itinerary of the thymic epithelium showing DE (Definitive Endoderm), AFE (Anterior Foregut Endoderm), 3PPE (Third Pharyngeal Pouch Endoderm) and TEP (Thymic Epithelial Progenitor) stages (Created in BioRender. Guillonneau, C. (2025) https://BioRender.com/r5v7uln ). b Factors tested in DOE (abbreviations), their associated pathways and the timings corresponding to each tested stage transition (D5-D7: DE-to-AFE, D7-D11: AFE-to-3PPE and D11-D13: 3PPE-to-TEP). Plackett–Burman designs were used to estimate factor effects on differentiation at the three transitions, with two dose levels (−1/+1) per factor. c UMAP representations of early ( Left ) and late ( Right ) pharyngeal development scRNA-seq reference datasets, with clusters corresponding to stages of the thymic differentiation trajectory shown in color. Reference datasets: Han et al. (E8.5–E9.5) and Magaletta et al. (E9.5–E12.5). d Bulk RNA-seq results for each sample (vertical) treated with combinations of factors tested in DOE in four experiments (D5-D7, Han E8.5; D7-D11, Han and Magaletta E9.5; D11-D13, Magaletta E11.5/12.5) showing expression scores of marker genes for pharyngeal development clusters (horizontal). Cluster names corresponding to the thymic differentiation trajectory are highlighted in bold. The upper part of each heatmap shows the factor combinations applied, with high doses highlighted in orange. Statistical significance was assessed by ANOVA (Supplementary Fig. ). Significant factors are shown in red or blue, indicating those to be supplemented or excluded in the optimized protocol. Han et. al. dataset: D5 to D7: p = 0.02338 (Noggin); 4.246e-05 (IWR1); 0.05526 (LY3); 4.345.e-07 (RA)/D7 to D11: p = 5.233.e-05 (CHIR99); 0.0002875 (FLI06); 0.0015895 (IWR1). Magaletta et. al. dataset: D7 to D11: p = 1.877.e-05 (CHIR99); 1.877.e-05 (FLI06); 0.0003179 (IRW1)/D11 to D13: dots indicate suggestive p values, p = 0.089927 (BMP4); 0.079926 (IGF1); 0.086185 (RANKL). e Summary of pathway modulation: black, DOE-identified pathways to be activated (+) or inhibited (−); blue, pathways neutral in DOE but enhancing FOXN1 expression (BMP/FGF) or proliferation (FGF/EGF) at the TEP stage; green, the FGF pathway (not tested in DOE, post-DOE), activating FOXN1 at the TEP stage. DE Definitive Endoderm, AFE Anterior Foregut Endoderm, 3PPE Third Pharyngeal Pouch Endoderm, TEP Thymic Epithelial Progenitor. See corresponding factor names in ( b ) (Created in BioRender. Guillonneau, C. (2025) https://BioRender.com/ht4edy0 ). f Summary of the optimized protocol with full factor list, doses and exposure windows, DE Definitive Endoderm, AFE Anterior Foregut Endoderm, 3PPE Third Pharyngeal Pouch Endoderm, TEP Thymic Epithelial Progenitor.

Article Snippet: The supplementation included Activin A, CHIR99, BMP4 (Miltenyi, 130-111-167), retinoic acid (Sigma Aldrich, 302-79-4), FGF8 (BiotechneR&D, 423-F8), Noggin (Miltenyi 130-103-455), LY-364947 (Sigma Aldrich L6293-5MG), FGF10 (Miltenyi, 130-127-858), IGF1 (Miltenyi, 130-093-886), EGF (Miltenyi, 130-097-751), and RANK-L (BiotechneR&D: 6449-TEC).

Techniques: RNA Sequencing, Expressing, Marker

Journal: Nature Communications

Article Title: Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

doi: 10.1038/s41467-025-68104-6

Figure Lengend Snippet: a UMAP plots of 12 macrophage and DC subtypes from baseline and follow-up samples. IGF1 ⁺Macrophage cluster (cluster 3) highlighted. b Volcano plot of DEGs in IGF1 ⁺ macrophages between baseline and follow-up. Upregulated (red), downregulated (blue), stable (grey) genes shown. c Bar plots of top enriched Reactome pathways in IGF1 ⁺ macrophages from DEGs (two-sided Wilcoxon rank-sum test, adjusted P values). Pathway enrichment of top 20 upregulated genes via Enrichr (Reactome_Pathways_2024, hypergeometric test, unadjusted P values). d UMAP plots of key marker gene expression ( HP , IGF1 , RETN ) in macrophage subsets; color intensity reflects normalized UMI counts. e Violin plots of IGF1 , RETN , HP expression across disease phases (EGPA baseline, Cs-remission, Cs-relapse) in macrophages. f Immunofluorescent staining and quantification of IGF1⁺CD68⁺ macrophages in bronchial mucosae (biological replicates; EGPA n = 15, Cs-remission n = 3, Cs-relapse n = 5). Scale bars: 100 μm (upper), 20 μm (lower). g UMAP plots of 11 epithelial cell subsets from combined samples. h Heatmap of relative enrichment (observed/expected Ro/e) of epithelial subtypes across groups and sample types. i Dot plot of reciprocal epithelial ligand-receptor expression across subsets. Interaction pairs linked by color-coded lines; dot size reflects expression fraction, color intensity shows relative expression. j Violin plots of marker gene expression for goblet cell subsets (Goblet-1, Goblet−2) and ionocytes across groups. k Immunofluorescent staining and quantification of MUC5AC⁺ epithelial cells (biological replicates; EGPA n = 10, Cs-remission n = 3, Cs-relapse n = 5). Scale bar: 100 μm. Data presented as median with IQR. f , k Two-sided Kruskal–Wallis test with Dunn’s post-hoc and Bonferroni correction. * P < 0.05, ** P < 0.01, *** P < 0.001; NS, not significant. Exact P values in Supplementary Data . Cs-relapse corticosteroid relapse, Cs-remission corticosteroid remission, DC dendritic cell, DEGs differentially expressed genes, IGF1 insulin-like growth factor 1, MUC5AC mucin 5AC, Ro/e ratio of observed to expected.

Article Snippet: For human sputum IGF1 concentration detection, 100uL sputum supernatant was used (Multi Sciences, Cat# EK1131-96).

Techniques: Marker, Gene Expression, Expressing, Staining

Journal: Nature Communications

Article Title: Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

doi: 10.1038/s41467-025-68104-6

Figure Lengend Snippet: a Immunofluorescent staining and quantification of IGF1⁺ epithelial cells at bronchial mucosae from control ( n = 6), SEA ( n = 9), EGPA ( n = 10), Cs-remission ( n = 3), and Cs-relapse ( n = 5) groups (biological replicates). Scale bar: 100 μm. b Bar plots of IGF1 concentrations in sputum samples from Control ( n = 13), SEA ( n = 23), and EGPA ( n = 21) (biological replicates). c Schematic of EGPA airway epithelial cells in ALI culture stimulated with IL-13, IL-33, or medium (Control). Bar plots show relative expression of IGF1 , IGF1R , and IGFBP3 , and IGF1 concentrations under different conditions. Data from 3 independent experiments (biological replicates). d Schematic of ALI system with IGF1 stimulation versus control. Representative histological (HE, PAS) and immunofluorescent (MUC5AC with DAPI) staining demonstrate morphological changes and mucin production (goblet hyperplasia) in ALI cultures with medium (Control) or IGF1 stimulation. Scale bars: 50 μm (HE, PAS), 20 μm (MUC5AC). Bar plots of IL-25, IL-33, and TSLP concentrations in culture supernatant at time points (Day 9, 13, 17, 21). Data from 3 independent experiments (biological replicates). e Scatter plot showing positive correlation between eosinophil abundance and IGF1 concentration in sputum from EGPA patients ( n = 21). f Schematic of proposed mechanism where IGF1 promotes goblet hyperplasia and augments T2-mediated inflammation through IGF1-IL25 loop, contributing to disease exacerbation in asthma and EGPA. Data presented as mean ± SD. a – c Two-sided one-way ANOVA with Tukey’s post-hoc test. d Two-sided unpaired t -test. e Two-sided Pearson correlation test. * P < 0.05, ** P < 0.01, *** P < 0.001; NS, not significant. Exact P values in Supplementary Data . ALI air-liquid interface, HE hematoxylin and eosin, IGF1R insulin-like growth factor 1 receptor, IGFBP3 insulin-like growth factor binding protein 3, PAS periodic acid-Schiff, TSLP thymic stromal lymphopoietin.

Article Snippet: For human sputum IGF1 concentration detection, 100uL sputum supernatant was used (Multi Sciences, Cat# EK1131-96).

Techniques: Staining, Control, Expressing, Concentration Assay, Binding Assay

Journal: Nature Communications

Article Title: Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

doi: 10.1038/s41467-025-68104-6

Figure Lengend Snippet: a – e Anti-IGF1 treatment reduces eosinophilic inflammation and airway remodeling in IL-5 transgenic mice challenged with HDM and IL-33. Mice were divided into Control (PBS-treated), Model (HDM+IL-33 challenged), and Anti-IGF1 (HDM+IL-33+anti-IGF1 antibody) groups. a Total cell counts in bronchoalveolar lavage fluid (BALF) from control, model, and anti-IGF1-treated groups. b Eosinophil percentage in BALF. c Absolute eosinophil counts in BALF. d IL−25 levels in BALF quantified by ELISA. e Representative histological images of lung sections stained with hematoxylin and eosin (H&E, upper panels) and periodic acid-Schiff (PAS, lower panels), with corresponding inflammation and PAS score quantifications. Scale bar, 100 μm. f – h IGF1R deficiency modulates eosinophilic inflammation and airway remodeling via IL−25 in HDM+IL-33 challenged mice. f Total cell counts in BALF from wild-type (WT, Scgb1a1 -IRES-+/+ Igf1r f/f ), conditional knockout ( Scgb1a1 -IRES-Cre/+ Igf1r f/f , CKO), and CKO mice treated with recombinant IL-25 (rIL-25). All groups were challenged with HDM+IL-33. g Flow cytometric analysis of eosinophils (CD45 + Siglec-F + CD11c - ) in BALF. Representative plots and quantification of eosinophil percentages are shown. h Representative H&E (upper panels) and PAS (lower panels) staining of lung sections from WT, CKO, and CKO+rIL-25 groups, with quantification of inflammation and PAS scores. Scale bar, 100 μm. Statistical analysis: Data are presented as mean ± SD ( n = 5 mice per group). Statistical significance was determined using a two-sided one-way ANOVA with Tukey’s post hoc test. * p < 0.05; ** p < 0.01; *** p < 0.001; NS, not significant. Exact P values and complete test statistics for a – h are provided in Supplementary Data . CKO conditional knockout, HDM house dust mite, rIL-25 recombinant IL-25, WT wild-type.

Article Snippet: For human sputum IGF1 concentration detection, 100uL sputum supernatant was used (Multi Sciences, Cat# EK1131-96).

Techniques: Transgenic Assay, Control, Enzyme-linked Immunosorbent Assay, Staining, Knock-Out, Recombinant