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.
Original language | English |
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Pages (from-to) | 2924 |
Journal | Nature Communications |
Volume | 4 |
DOIs | |
Publication status | Published - 2013 |
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