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Nat Commun. 2013;4:2924. doi: 10.1038/ncomms3924.

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.

Author information

1
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
2
Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
3
Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute, Cambridge CB2 OXY, UK.
4
Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Ingolstaedter Landstrasse 1 85764 Neuherberg, Germany.
5
Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
6
Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
#
Contributed equally

Abstract

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.

PMID:
24326267
PMCID:
PMC4362711
DOI:
10.1038/ncomms3924
[Indexed for MEDLINE]
Free PMC Article

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