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Charting endocrine progenitors across species and organs

ABSTRACT: Hormone-producing cells in the pancreas and intestine regulate whole-body metabolism and are key targets for causal therapies for diabetes and obesity. A deeper understanding of endocrine lineage formation (endocrinogenesis) in these organs is essential to elucidate disease mechanisms and develop improved therapies. Here, we performed cross-species (mouse-human) and cross-system (in vivo-in vitro) comparisons of pancreatic endocrine progenitors (EPs), complemented by cross-organ (pancreas-intestine) analyses, using single-cell transcriptomics and epigenomics integrated with bulk proteomics. We uncovered shared and distinct gene regulatory networks (GRNs) and cell-cell communication patterns during lineage allocation across species, systems, and organs. Additionally, we identified cardiometabolic risk-associated genes restricted to embryonic pancreatic EPs but largely absent in the adult pancreas, implicating developmental origins of disease. Furthermore, our integrated, multi-source EP profiling resolved the transcriptional programs underlying off-target enterochromaffin cell formation during in vitro differentiation toward human islet cells. Finally, we revealed conserved, dynamic shifts in programs governing the cell cycle, mRNA translation, and cytoskeletal organization during endocrinogenesis. Collectively, this multi-source EP profiling establishes a resource that charts the molecular landscape of endocrinogenesis and informs therapies for metabolic disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE342091 | GEO | 2026/09/01

REPOSITORIES: GEO

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Charting endocrine progenitors across species and organs

Project description:Hormone-producing cells in the pancreas and intestine regulate whole-body metabolism and are key targets for causal therapies for diabetes and obesity. A deeper understanding of endocrine lineage formation (endocrinogenesis) in these organs is essential to elucidate disease mechanisms and develop improved therapies. Here, we performed cross-species (mouse-human) and cross-system (in vivo-in vitro) comparisons of pancreatic endocrine progenitors (EPs), complemented by cross-organ (pancreas-intestine) analyses, using single-cell transcriptomics and epigenomics integrated with bulk proteomics. We uncovered shared and distinct gene regulatory networks (GRNs) and cell-cell communication patterns during lineage allocation across species, systems, and organs. Additionally, we identified cardiometabolic risk-associated genes restricted to embryonic pancreatic EPs but largely absent in the adult pancreas, implicating developmental origins of disease. Furthermore, our integrated, multi-source EP profiling resolved the transcriptional programs underlying off-target enterochromaffin cell formation during in vitro differentiation toward human islet cells. Finally, we revealed conserved, dynamic shifts in programs governing the cell cycle, mRNA translation, and cytoskeletal organization during endocrinogenesis. Collectively, this multi-source EP profiling establishes a resource that charts the molecular landscape of endocrinogenesis and informs therapies for metabolic disease.

2026-08-25 | PXD076279 | Pride

Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans

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