Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta

Chloé S Baron, Lennart Kester, Anna Klaus, Jean-Charles Boisset, Roshana Thambyrajah, Laurent Yvernogeau, Valérie Kouskoff, Georges Lacaud, Alexander van Oudenaarden, Catherine Robin

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders.

Original languageEnglish
Pages (from-to)2517
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 28 Jun 2018

Keywords

  • Animals
  • Aorta/cytology
  • Cell Differentiation
  • Cell Lineage
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Ontology
  • Gene Regulatory Networks
  • Hemangioblasts/cytology
  • Hematopoietic Stem Cells/cytology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Annotation
  • Single-Cell Analysis
  • Transcriptome

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