Vasculogenesis, a story of glycome and transcriptomal regulation

Abstract

Impaired vascularization is implicated in diverse pathological conditions such as cardiac ischemia. Therapeutic vasculogenesis is an emerging concept that can be harnessed to treat this condition, contingent upon better molecular understanding. We evaluated the contribution of the microenvironment during vasculogenesis by modifying heparan sulfate gycosaminoglycans (HSGAGs) using a pharmacologic‐genetic approach. Using an embryoid body model, we show that the de novo development of endothelial cells correlates with an increase in the HSGAG‐sulfating enzyme N‐deacetylase‐N‐sulfotransferase‐1 (NDST1) and that inhibiting HSGAGs blocked vasculogenesis. Similarly, in zebrafish embryos, NDST1 knock‐down resulted in a significantly impaired vasculature. To explore the cross‐talk between the glycocalyx and the cellular transcriptome during vasculogenesis, we identified gene expression patterns that are distinct between wild‐type and NDST1‐knock down zebrafish embryos at stages critical for vasculogenesis. Our analyses revealed an emerging picture of a cascade of pathways downstream of the glycocalyx that are intricately connected to cell signaling, matrix, cell survival/apoptosis and cell fate determination.