A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
Publication Year 2020-10-19,Volume 21,Issue #12,Page 1574-1584
Journal Title
Nature Immunology
Publication Type
Journal Article
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.
WEHI Research Division(s)
Blood Cells And Blood Cancer; Immunology; Epigenetics And Development
PubMed ID
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Creation Date: 2021-02-01 12:05:21
Last Modified: 2021-03-02 10:38:57
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