Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression

Patrick Coulombe, Grace Cole, Amanda Fentiman, Jeremy D. K. Parker, Eric Yung, Misha Bilenky, Lemlem Degefie, Patrick Lac, Maggie Y. M. Ling, Derek Tam, R. Keith Humphries and Aly Karsan ()
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Patrick Coulombe: BC Cancer
Grace Cole: BC Cancer
Amanda Fentiman: BC Cancer
Jeremy D. K. Parker: BC Cancer
Eric Yung: BC Cancer
Misha Bilenky: BC Cancer
Lemlem Degefie: BC Cancer
Patrick Lac: BC Cancer
Maggie Y. M. Ling: BC Cancer
Derek Tam: BC Cancer
R. Keith Humphries: BC Cancer
Aly Karsan: BC Cancer

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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 define the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identify 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 impairs the formation of functional Runx1-expressing HE which significantly impedes the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells.

Date: 2023
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DOI: 10.1038/s41467-023-40283-0

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