Pluto Bioinformatics

GSE115311: CRISPR/Cas9-mediated Gene Knockout Reveals a Guardian Role of NF-kB/RelA in Maintaining the Homeostasis of Human Vascular Cells

Bulk RNA sequencing

Dysfunction of blood vessels leads to severe vasculature pathogenesis. Previous studies have demonstrated that constitutive NFB activation results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NFB regulates blood vessel homeostasis remains largely elusive. Here, using CRISPR/Cas9-mediated gene editing, we generated RelA knockout human embryonic stem cells (hESCs) and differentiated them into human vascular derivatives to study how NFB modulates vascular cells under basal and inflammatory conditions. Multi-dimensional phenotypic assessments and transcriptomic analyses revealed that RelA deficiency affected vascular cells via modulating vascular inflammation, survival, vasculogenesis, differentiation and extracellular matrix organization in a cell type-specific manner under basal condition, and that RelA protected vascular cells against apoptosis and modulated vascular inflammatory response upon TNF stimuli. Lastly, further evaluation of gene expression patterns in IB knockout vascular cells demonstrated that IB acted largely independent of NFB signaling pathway. Taken together, our data reveals a protective role of NFB/RelA in modulating human blood vessel homeostasis and maps the human vascular transcriptomic landscapes for the discovery of novel therapeutic targets. SOURCE: Zunpeng Liu (zunpengliu@163.com) - Jing Qu State Key Laboratory of Stem Cell and Reproductive Biology