Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells

Nat Immunol. 2018 Jan;19(1):85-97. doi: 10.1038/s41590-017-0001-2. Epub 2017 Nov 21.

Abstract

The hierarchy of human hemopoietic progenitor cells that produce lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations produce lymphoid and myeloid cells, but they remain incompletely characterized. Here we demonstrated that lympho-myeloid progenitor populations in cord blood - lymphoid-primed multi-potential progenitors (LMPPs), granulocyte-macrophage progenitors (GMPs) and multi-lymphoid progenitors (MLPs) - were functionally and transcriptionally distinct and heterogeneous at the clonal level, with progenitors of many different functional potentials present. Although most progenitors had the potential to develop into only one mature cell type ('uni-lineage potential'), bi- and rarer multi-lineage progenitors were present among LMPPs, GMPs and MLPs. Those findings, coupled with single-cell expression analyses, suggest that a continuum of progenitors execute lymphoid and myeloid differentiation, rather than only uni-lineage progenitors' being present downstream of stem cells.

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cell Separation / methods
  • Cells, Cultured
  • Gene Expression Profiling / methods*
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Lymphoid Progenitor Cells / metabolism*
  • Mice
  • Myeloid Progenitor Cells / metabolism*
  • Single-Cell Analysis / methods*
  • Transplantation, Heterologous