UNDERSTANDING EARLY HEMATOPOIETIC DEVELOPMENT IN THE MOUSE EMBRYO

Abstract

Hematopoietic stem cells (HSCs) hold great promise for therapeutics. To further unravel their developmental processes, we focused on early hematopoiesis. This begins in the yolk sac (YS) and para-aortic splanchnopleura (P-Sp), which later forms the HSC-containing aorta-gonad-mesonephros (AGM). YS and P-Sp hemangioblast-derived colonies were found to have similar transcriptome profiles despite their distinct hematopoietic potentials. Transcriptome analysis of E8.5 primitive streak as it acquires hematopoietic potential identified <i>Pcgf5</i>, a member of the Polycomb group ring finger (Pcgf) family involved in Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic silencing. ChIP-seq of PRC1 in <i>in vitro</i>-derived populations that recapitulate YS and P-Sp hematopoiesis identified known and novel targets, and revealed that PRC1 variants regulate distinct targets during hematopoiesis. We also identified 2 <i>de novo</i> sequence motifs shared by PRC1 components, and propose a mammalian PRC1 recruitment method. Together, these results highlight the complexity of lineage specification and epigenetic regulation during early hematopoietic development.