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Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Original publication

DOI

10.1038/ncomms3924

Type

Journal article

Journal

Nat Commun

Publication Date

2013

Volume

4

Keywords

Animals, Core Binding Factor Alpha 2 Subunit, Embryo, Mammalian, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Hemangioblasts, Male, Mice, Mice, Transgenic, Pregnancy, Single-Cell Analysis