A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics
- Amann-Zalcenstein, D; Tian, L; Schreuder, J; Tomei, S; Lin, DS; Fairfax, KA; Bolden, JE; McKenzie, MD; Jarratt, A; Hilton, A; Jackson, JT; Di Rago, L; McCormack, MP; de Graaf, CA; Stonehouse, O; Taoudi, S; Alexander, WS; Nutt, SL; Ritchie, ME; Ng, AP; Naik, SH;
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
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:05:21Last Modified: 2021-03-02 10:38:57