Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing

Research output: Contribution to journalArticle

Abstract

According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, with the notable exception that both pathways are proposed to generate all myeloid innate immune cell types through the same myeloid-restricted pre-granulocyte-macrophage progenitor (pre-GM) (Lin(-)Sca-1(-)c-Kit(+)CD41(-)FcγRII/III(-)CD150(-)CD105(-)). By single-cell transcriptome profiling of pre-GMs, we identified distinct myeloid differentiation pathways: a pathway expressing the gene encoding the transcription factor GATA-1 generated mast cells, eosinophils, megakaryocytes and erythroid cells, and a pathway lacking expression of that gene generated monocytes, neutrophils and lymphocytes. These results identify an early hematopoietic-lineage bifurcation that separates the myeloid lineages before their segregation from other hematopoietic-lineage potential.

Details

Authors
  • Roy Drissen
  • Natalija Buza-Vidas
  • Petter Woll
  • Supat Thongjuea
  • Adriana Gambardella
  • Alice Giustacchini
  • Elena Mancini
  • Alya Zriwil
  • Michael Lutteropp
  • Amit Grover
  • Adam Mead
  • Ewa Sitnicka
  • Sten Eirik W Jacobsen
  • Claus Nerlov
Organisations
External organisations
  • University of Oxford
  • University of Edinburgh
  • European Molecular Biology Laboratory
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology
Original languageEnglish
Pages (from-to)666-676
JournalNature Immunology
Volume17
Issue number6
Early online date2016 Apr 4
Publication statusPublished - 2016 Jun
Publication categoryResearch
Peer-reviewedYes