Szlachcic, Wojciech JLetai, Katherine CScavuzzo, MarissaBorowiak, Małgorzata2024-03-142024-03-142023-03-04BioEssays, 45, e2200186https://hdl.handle.net/10593/27675This is the Accepted Version of the following article: Szlachcic, W. J., Letai, K. C., Scavuzzo, M. A., & Borowiak, M. (2023). Deep into the niche: Deciphering local endoderm-microenvironment interactions in development, homeostasis, and disease of pancreas and intestine. BioEssays, 45, e2200186, which has been published at https://doi.org/10.1002/bies.202200186. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy [http://www.wileyauthors.com/self-archiving]. The read-only version of Final Published Version can be accessed here: https://onlinelibrary.wiley.com/share/author/3J48826BWNJ6KJPECKIR?target=10.1002/bies.202200186Unraveling molecular and functional heterogeneity of niche cells within the developing endoderm could resolve mechanisms of tissue formation and maturation. Here, we discuss current unknowns in molecular mechanisms underlying key developmental events in pancreatic islet and intestinal epithelial formation. Recent breakthroughs in single-cell and spatial transcriptomics, paralleled with functional studies in vitro, reveal that specialized mesenchymal subtypes drive the formation and maturation of pancreatic endocrine cells and islets via local interactions with epithelium, neurons and microvessels. Analogous to this, distinct intestinal niche cells regulate both epithelial development and homeostasis throughout life. We propose how this knowledge can be used to progress research in the human context using pluripotent stem cell-derived multilineage organoids. Overall, understanding the interactions between the multitude of microenvironmental cells and how they drive tissue development and function could help us make more therapeutically relevant in vitro models.en-USAttribution 4.0 Internationalgut developmenthumanin vitro differentiationmicroenvironmentorganoidspancreas developmentpluripotent stem cellsinfo:eu-repo/semantics/preprint