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.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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