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Transcriptome analysis reveals microvascular endothelial cell-dependent pericyte differentiation.


ABSTRACT: Microvascular homeostasis is strictly regulated, requiring close interaction between endothelial cells and pericytes. Here, we aimed to improve our understanding of how microvascular crosstalk affects pericytes. Human-derived pericytes, cultured in absence, or presence of human endothelial cells, were studied by RNA sequencing. Compared with mono-cultured pericytes, a total of 6704 genes were differentially expressed in co-cultured pericytes. Direct endothelial contact induced transcriptome profiles associated with pericyte maturation, suppression of extracellular matrix production, proliferation, and morphological adaptation. In vitro studies confirmed enhanced pericyte proliferation mediated by endothelial-derived PDGFB and pericyte-derived HB-EGF and FGF2. Endothelial-induced PLXNA2 and ACTR3 upregulation also triggered pericyte morphological adaptation. Pathway analysis predicted a key role for TGF? signaling in endothelial-induced pericyte differentiation, whereas the effect of signaling via gap- and adherens junctions was limited. We demonstrate that endothelial cells have a major impact on the transcriptional profile of pericytes, regulating endothelial-induced maturation, proliferation, and suppression of ECM production.

SUBMITTER: Brandt MM 

PROVIDER: S-EPMC6821775 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Transcriptome analysis reveals microvascular endothelial cell-dependent pericyte differentiation.

Brandt Maarten M MM   van Dijk Christian G M CGM   Maringanti Ranganath R   Chrifi Ihsan I   Kramann Rafael R   Verhaar Marianne C MC   Duncker Dirk J DJ   Mokry Michal M   Cheng Caroline C  

Scientific reports 20191030 1


Microvascular homeostasis is strictly regulated, requiring close interaction between endothelial cells and pericytes. Here, we aimed to improve our understanding of how microvascular crosstalk affects pericytes. Human-derived pericytes, cultured in absence, or presence of human endothelial cells, were studied by RNA sequencing. Compared with mono-cultured pericytes, a total of 6704 genes were differentially expressed in co-cultured pericytes. Direct endothelial contact induced transcriptome prof  ...[more]

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