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Pré-Publication, Document De Travail Année : 2023

A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation.

Résumé

The pancreas is a critical endocrine and exocrine dual gland. While pancreas organoid models have been extensively explored for medical applications ranging from metabolic to oncologic conditions, there are still gaps in our understanding of the normal developmental trajectories of pancreatic cells during in vivo human ontogenesis. Here we mapped their spatial and chronological dynamics using 3D imaging of cleared human embryonic and fetal pancreases. Unexpectedly, we detected insulin immune-positive cells as soon as 5 post-conceptional weeks, two weeks earlier than previously observed. We identified a central niche as the onset of the earliest insulin cells production, and detected extra-pancreatic loci within the adjacent developing gut. Conversely, proliferating pancreatic progenitors were located in the periphery of the epithelium, suggesting the existence of two separated pancreatic niches for differentiation and proliferation. We next validated an explant culture system enabling in vitro proliferation of pancreatic progenitors. This unveiled a mitogenic effect of PDGFAA in progenitors acting through the pancreatic mesenchyme. Overall, this works presents a first 3D atlas of the human developing pancreas charting both endocrine and proliferating cells across early development.
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Dates et versions

hal-04302461 , version 1 (27-11-2023)

Identifiants

  • HAL Id : hal-04302461 , version 1

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Adrian Villalba, Yorick Gitton, Megumi Inoue, Virginie Aiello, Raphaël Blain, et al.. A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation.. 2023. ⟨hal-04302461⟩
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