First Author | Amann-Zalcenstein D | Year | 2020 |
Journal | Nat Immunol | Volume | 21 |
Issue | 12 | Pages | 1574-1584 |
PubMed ID | 33077975 | Mgi Jnum | J:305848 |
Mgi Id | MGI:6706598 | Doi | 10.1038/s41590-020-0799-x |
Citation | Amann-Zalcenstein D, et al. (2020) A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics. Nat Immunol 21(12):1574-1584 |
abstractText | 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. |