ArticleNature communications2022
Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Charting Endocrine Progenitors Across Species and Organs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CTNNB1 Genetic Variation and Its Interaction With DLK1 in Type 2 Diabetes Mellitus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury.Communications biology · 2026Article
- Epigenetic control of PDX1 and NGN3 by a computationally designed PRC2 inhibitor enforces pancreatic endocrine differentiation from pluripotent stem cells.Research square · 2026Article
- Efficient control of enterochromaffin versus islet differentiation from human pluripotent stem cell-derived pancreatic progenitors.Nature communications · 2026Article
- Impaired insulin secretion via the Wnt5a/β-catenin pathway contributes to diabetes development in pancreatic cancer.Experimental & molecular medicine · 2026Article
- Human pluripotent stem cell models of Friedreich's ataxia: innovations, considerations, and future perspectives.Stem cell research & therapy · 2026Review
- Oxidative stress and GPX2 control pancreatic vs. non-pancreatic cell fate in human endoderm.Nature communications · 2026Article
- Naphthoquinones mediate differentiation of human umbilical cord derived mesenchymal stem cells into insulin producing cells through regulation of Wnt and BMP pathways.BioImpacts : BI · 2026Article
- Comparative β-cell development: insights from Rodents, humans and induced pluripotent stem cell models.Stem cell research & therapy · 2025Review
- Spatially organized cellular communities shape functional tissue architecture in the pancreas.Science advances · 2025Article
- Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression.Science advances · 2025Article
- The role of JNK signaling pathway in organ fibrosis.Journal of advanced research · 2025Review
- Improved Differentiation Towards Insulin Producing Beta-Cells Derived from Healthy Canine Pancreatic Ductal Organoids.Veterinary sciences · 2025Article
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation.Cellular and molecular life sciences : CMLS · 2025Article
- INS2 lineage cell tracking and insulin expression in the related organs of mice.Scientific reports · 2025Article
- Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets.Nature communications · 2025Article
- Pancreatic organogenesis mapped through space and time.Experimental & molecular medicine · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In vitro derivation of pancreatic β-cells from human pluripotent stem cells holds promise as diabetes treatment. Despite recent progress, efforts to generate physiologically competent β-cells are still hindered by incomplete understanding of the microenvironment's role in β-cell development and maturation. Here, we analyze the human mesenchymal and endothelial primary cells from weeks 9-20 fetal pancreas and identify a time point-specific microenvironment that permits β-cell differentiation. Further, we uncover unique factors that guide in vitro development of endocrine progenitors, with WNT5A markedly improving human β-cell differentiation. WNT5A initially acts through the non-canonical (JNK/c-JUN) WNT signaling and cooperates with Gremlin1 to inhibit the BMP pathway during β-cell maturation. Interestingly, we also identify the endothelial-derived Endocan as a SST+ cell promoting factor. Overall, our study shows that the pancreatic microenvironment-derived factors can mimic in vivo conditions in an in vitro system to generate bona fide β-cells for translational applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.