GSE196047
Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression
Hematopoietic stem and progenitor cells (HSPCs) originate from an endothelial-to-hematopoietic transition (EHT) during embryogenesis. Characterization of early hemogenic endothelial (HE) cells is required to understand what drives hemogenic specification and to accurately define cells capable of undergoing EHT. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we defined the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identified the transcription factor Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression. Meis1 is expressed at the earliest stages of EHT and distinguishes pre-HE cells primed towards the hemogenic trajectory from the arterial endothelial cells that continue towards a vascular fate. Endothelial-specific deletion of Meis1 impaired the formation of functional Runx1-expressing HE which significantly impeded the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells. Overall design: CD31+CD117-CD45-Runx1+23GFP- cells were FACS-isolated from Runx1+23GFP transgenic embryos and compared to bulk EC FACS-isolated from WT littermates