Pancreatic acinar differentiation is guided by differential laminin deposition

Scientific Reports
Charlotte HeymansChristophe E Pierreux

Abstract

Endothelial cells play multiple roles during pancreas organogenesis. First, they are required to instruct endoderm-derived pancreatic progenitor cells to initiate branching morphogenesis. Later, blood vessels promote β-cell differentiation but also limit acinar development. In this work, we show how endothelial cells might signal to pancreatic progenitors and spatially regulate acinar differentiation. Using an ex vivo culture system of undifferentiated E12.5 pancreata, we demonstrate that embryonic endothelial progenitor cells and their conditioned medium prevent the expression of two members of the pro-acinar transcriptional PTF1L-complex. This effect is not mediated by SPARC, a protein abundantly released in the medium conditioned by endothelial progenitors. On the contrary, heterotrimeric laminin-α1β1γ1, also produced by endothelial progenitor cells, can repress acinar differentiation when used on its own on pancreatic explants. Lastly, we found that laminin-α1 is predominantly found in vivo around the pancreatic trunk cells, as compared to the tip cells, at E14.5. In conclusion, we propose that expression or deposition of laminin-α1β1γ1 around the trunk cells, where blood vessels are predominantly localized, prevent acinar ...Continue Reading

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Citations

Nov 13, 2019·Journal of Morphology·Magdalena Kowalska, Weronika Rupik
Apr 16, 2021·Metabolism: Clinical and Experimental·Anna GoddiRonald N Cohen
Apr 25, 2021·Mathematical Biosciences and Engineering : MBE·Dasong Huang, Ruiqi Wang
Aug 29, 2020·Developmental Cell·Corinna CozzitortoFrancesca M Spagnoli

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Methods Mentioned

BETA
transgenic
fluorescence imaging
PCR
dissection

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