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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.

Item Type:	Article
Authors/Creators:	Amann-Zalcenstein, D and Tian, Luyi and Schreuder, J and Tomei, S and Lin, DS and Fairfax, KA and Bolden, JE and McKenzie, MD and Jarratt, A and Hilton, A and Jackson, JT and Di Rago, L and McCormack, MP and de Graaf, CA and Stonehouse, O and Taoudi, S and Alexander, WS and Nutt, SL and Ritchie, ME and Ng, AP and Naik, SH
Journal or Publication Title:	Nature Immunology
Publisher:	Nature Publishing Group
ISSN:	1529-2908
DOI / ID Number:	https://doi.org/10.1038/s41590-020-0799-x
Copyright Information:	Copyright 2020 Nature Publishing Group
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