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Communication Dans Un Congrès Année : 2023

A 3D atlas of the human embryonic and fetal pancreas to study proliferation and differentiation of multipotent pancreatic progenitors

Villalba Adrian
  • Fonction : Auteur
Yorick Gitton
Aiello Virginie
  • Fonction : Auteur
Inoue Megumi
  • Fonction : Auteur
Toupin Maryne
  • Fonction : Auteur
Mazaud-Guittot Severine
  • Fonction : Auteur
Chédotal Alain
  • Fonction : Auteur
Scharfmann Raphaël
  • Fonction : Auteur

Résumé

The study of human fetal pancreas development offers valuable insights into the intricate processes governing pancreatic cell proliferation and differentiation. In this research, we employ an innovative approach integrating tissue clearing, in toto labeling, and light-sheet fluorescence microscopy to construct a three-dimensional atlas of the human embryonic and fetal pancreas during the first trimester of pregnancy. We show that first INS+ cells appear around 5 post-conception weeks, much before it was previously determined by conventional immunostaining. They are restricted to the inner part of the organ as well as other endocrine subsets like GCG+ and SST+ cells. Conversely, proliferating pancreatic progenitors are located in the periphery of the epithelium, suggesting the existence of two separated pancreatic niches for differentiation and proliferation. We also found that acinar CPA1+ cells are preferentially found in the peripheral region of the embryonic and fetal pancreas, even these differentiated cells do not display proliferation ability. Additionally, the existence of extra pancreatic INS+ cells adjacent to the gut was confirmed. On top of that, an explant culture system was developed 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 the most complete atlas of the human developing pancreas charting both endocrine and proliferating cells across early development. These novel insights contribute to a deeper comprehension of developmental biology and hold promise for advancing regenerative medicine and therapeutic interventions.
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Dates et versions

hal-04237985 , version 1 (11-10-2023)

Identifiants

  • HAL Id : hal-04237985 , version 1

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Villalba Adrian, Yorick Gitton, Aiello Virginie, Inoue Megumi, Toupin Maryne, et al.. A 3D atlas of the human embryonic and fetal pancreas to study proliferation and differentiation of multipotent pancreatic progenitors. RegenBell symposium BARCELONA 2023, Nov 2023, BARCELONA, Spain. ⟨hal-04237985⟩
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