Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells

Chris Sebastiaan Vink, Fernando Jose Calero-Nieto, Xiaonan Wang, Antonio Maglitto, Samanta Antonella Mariani, Wajid Jawaid, Berthold Göttgens, Elaine Dzierzak

Research output: Contribution to journalArticlepeer-review

Abstract

Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single cell transcriptomics and functional analyses to connect HSC identity to specific gene expression.
Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit and CD27 phenotypic parameters that associate specific
molecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.
Original languageEnglish
Article number107627
JournalCell Reports
Volume31
Issue number6
DOIs
Publication statusPublished - 12 May 2020

Keywords

  • AGM
  • CD27
  • Gata2
  • development
  • embryo
  • functional identity
  • hematopoietic stem cell
  • heterogeneity
  • intra-aortic hematopoietic clusters
  • single-cell transcriptome
  • transplantation

Fingerprint Dive into the research topics of 'Iterative single-cell analyses define the transcriptome of the first functional hematopoietic stem cells'. Together they form a unique fingerprint.

Cite this