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

作者:Drissen Roy; Buza Vidas Natalija; Woll Petter; Thongjuea Supat; Gambardella Adriana; Giustacchini Alice; Mancini Elena; Zriwil Alya; Lutteropp Michael; Grover Amit; Mead Adam; Sitnicka Ewa; Jacobsen Sten Eirik W*; Nerlov Claus*
来源:Nature Immunology, 2016, 17(6): 666-+.
DOI:10.1038/ni.3412

摘要

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(-)Fc gamma RII/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.

  • 出版日期2016-6