Swiers, G.* ; Baumann, C.* ; O'Rourke, J.* ; Giannoulatou, E.* ; Taylor, S.* ; Joshi, A.* ; Moignard, V.* ; Pina, C.* ; Bee, T.* ; Kokkaliaris, K.D. ; Yoshimoto, M.* ; Yoder, M.C.* ; Frampton, J.* ; Schroeder, T. ; Enver, T.* ; Göttgens, B.* ; de Bruijn, M.F.*
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
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Editors
Keywords
Hematopoietic Stem-cells; Definitive Hematopoiesis; Mouse Embryo; Aortic Endothelium; Runx1 Expression; Fetal Liver; Agm Region; Lymphohematopoietic Cells; Differentiation Cultures; Blood Progenitors
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Language
english
Publication Year
2013
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2013
ISSN (print) / ISBN
2041-1723
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2041-1723
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Article Number: 2924
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Nature Publishing Group
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London
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Peer reviewed
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-501200-001
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Erfassungsdatum
2013-12-17