HDAC1 and HDAC2 regulates TGF-b during Endothelial-to-Hematopoietic Transition [ChIP-Seq]

The first hematopoietic stem cells originate from hemogenic endothelium (HE), that trans-differentiate into the lumen to form hematopoietic clusters. The molecular mechanisms driving this transition are only poorly understood. Here, we present a complete and comprehensive study that shows the requirement for Transforming Growth Factor beta (Tgfbeta) signalling as the master regulator of triggering EHT from HE, including Runx1-/- HE. We employed RNA-Seq data on Hdac deficient HE, together with ChIP-Seq for HDAC1 and HDAC2 and on wild type HE that indicated its importance in EHT. We tested our findings extensively on HE derived from different sites/origin. In all instances we observed an increase in the frequency of EHT by decreasing Tgfbeta levels. ChIP-sequencing for Hdac1 and Hdac2 in HE populations derived from three different cell lines