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Dual function of perivascular fibroblasts in vascular stabilization in zebrafish


Autoři: Arsheen M. Rajan aff001;  Roger C. Ma aff001;  Katrinka M. Kocha aff001;  Dan J. Zhang aff002;  Peng Huang aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada aff001;  Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada aff002
Vyšlo v časopise: Dual function of perivascular fibroblasts in vascular stabilization in zebrafish. PLoS Genet 16(10): e1008800. doi:10.1371/journal.pgen.1008800
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008800

Souhrn

Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts markedly reduces collagen deposition around endothelial cells, resulting in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.

Klíčová slova:

Blood vessels – Cell differentiation – Collagens – Fibroblasts – Hemorrhage – Heterozygosity – Pericytes – Zebrafish


Zdroje

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