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

Research output: Contribution to journalArticle

Authors

  • 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
  • Timm Schroeder
  • Tariq Enver
  • Berthold Göttgens
  • Marella F T R de Bruijn

Colleges, School and Institutes

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.

Details

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