A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
- 19 October 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 21 (12), 1574-1584
- https://doi.org/10.1038/s41590-020-0799-x
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.Keywords
Funding Information
- Department of Health | National Health and Medical Research Council (GNT0637403, GNT1113577, GNT1058344, GNT1155342, GNT1062820, GNT1085765, GNT0516782, GNT1124812)
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