The versican-hyaluronan complex provides an essential extracellular matrix niche for Flk1+ precursors in vasculogenesis and primitive hematopoiesis [article]

Sumeda Nandadasa, Anna O'Donnell, Ronald J Midura, Suneel S Apte
2019 bioRxiv   pre-print
Extracellular matrix aggregates comprising the proteoglycan versican and glycosaminoglycan hyaluronan are necessary for cardiac development. Here we identify failure of primary vascular plexus formation and attenuation of primitive hematopoiesis in the yolk sac of the mouse insertional mutant Vcanhdf, which lacks all versican isoforms. Spatially co-regulated versican and hyaluronan were intimately associated with Flk1+ hematovascular progenitor cells migrating from the primitive streak into
more » ... ive streak into extraembryonic mesoderm, although not with the differentiated successors. In the absence of versican, yolk sac and embryo hyaluronan were severely depleted, suggesting that versican stabilizes extracellular hyaluronan. Vcan inactivation by CRISPR/Cas9 in mouse embryonic stem cells reduced expression of vascular endothelial and hematopoiesis markers in embryoid bodies, which formed fewer and shorter vascular sprouts in response to VEGF165 and fewer blood colonies. These findings, together with single-cell transcriptome data, suggest that versican-hyaluronan pericellular matrix provides a crucial niche for hematovascular progenitors immediately after their genesis at gastrulation.
doi:10.1101/753418 fatcat:322g7normzeg5o2vxn7kyhebs4