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Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.
Nat. Commun. 4:2924 (2013)
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hematopoietic Stem-cells; Definitive Hematopoiesis; Mouse Embryo; Aortic Endothelium; Runx1 Expression; Fetal Liver; Agm Region; Lymphohematopoietic Cells; Differentiation Cultures; Blood Progenitors
Institute(s) Research Unit Stem Cell Dynamics (SCD)