RT Journal Article
SR Electronic
T1 Identification and implication of tissue-enriched ligands in epithelial-endothelial crosstalk during pancreas development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.19.488467
DO 10.1101/2022.04.19.488467
A1 Manon Moulis
A1 Steve Vincent Maurice Runser
A1 Laura Glorieux
A1 Nicolas Dauguet
A1 Christophe Vanderaa
A1 Laurent Gatto
A1 Donatienne Tyteca
A1 Patrick Henriet
A1 Francesca M. Spagnoli
A1 Dagmar Iber
A1 Christophe E. Pierreux
YR 2022
UL http://biorxiv.org/content/early/2022/04/19/2022.04.19.488467.abstract
AB Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. Bmp7 and Wnt7b, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and Sema6d, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced Bmp7 restrained development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of Bmp7 in the intercellular communications shaping vessel development during pancreas organogenesis.Competing Interest StatementThe authors have declared no competing interest.