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

Gemma Swiers, Claudia Baumann, John O'Rourke, Eleni Giannoulatou, Stephen Taylor, Anagha Joshi, Victoria Moignard, Cristina Pina, Thomas Bee, Konstantinos D Kokkaliaris, Momoko Yoshimoto, Mervin C Yoder, Jon Frampton, Timm Schroeder, Tariq Enver, Berthold Göttgens, Marella F T R de Bruijn

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)2924
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 2013

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