Histone H2A deubiquitinase BAP1 is essential for endothelial cell differentiation from human pluripotent stem cells

Abstract

Polycomb group proteins (PcGs) add repressive post translational histone modifications such as H2AK119ub1, and histone H2A deubiquitinases remove it. Mice lacking histone H2A deubiquitinases such as Usp16 and Bap1 die in embryonic stage, while mice lacking Usp3, Mysm1, Usp12, and Usp21 have been shown to be deficient in hematopoietic lineage differentiation, cell cycle regulation, and DNA repair. Thus, it is likely that histone deubiquitinases may also be required for human endothelial cell differentiation; however, there are no reports about the role of histone H2A deubiquitinase BAP1 in human endothelial cell development. We differentiated human pluripotent stem cells into the endothelial lineage which expressed stable inducible shRNA against BAP1. Our results show that BAP1 is required for human endothelial cell differentiation.