A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics

Nat Immunol. 2020 Dec;21(12):1574-1584. doi: 10.1038/s41590-020-0799-x. Epub 2020 Oct 19.

Abstract

A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Lin-c-Kit+Sca-1+Flt3+ cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1 and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1-GFP reporter mice, we identify a transcriptionally and functionally unique Dach1-GFP- subpopulation within LMPPs with lymphoid potential with low to negligible classic myeloid potential. We term these 'lymphoid-primed progenitors' (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers*
  • Cells, Cultured
  • Computational Biology / methods
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Gene Expression Profiling
  • Genomics* / methods
  • Hematopoiesis / genetics
  • High-Throughput Nucleotide Sequencing
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / immunology
  • Lymphoid Progenitor Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Proteomics
  • Single-Cell Analysis* / methods

Substances

  • Biomarkers
  • Dach1 protein, mouse
  • Eye Proteins