A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics

Daniela Amann-Zalcenstein, Luyi Tian, Jaring Schreuder, Sara Tomei, Dawn S. Lin, Kirsten A. Fairfax, Jessica E. Bolden, Mark D. McKenzie, Andrew Jarratt, Adrienne Hilton, Jacob T. Jackson, Ladina Di Rago, Matthew P. McCormack, Carolyn A. de Graaf, Olivia Stonehouse, Samir Taoudi, Warren S. Alexander, Stephen L. Nutt, Matthew E. Ritchie, Ashley P. NgShalin H. Naik

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Linc-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.

Original languageEnglish
Pages (from-to)1574-1584
Number of pages11
JournalNature Immunology
Volume21
Issue number12
DOIs
Publication statusPublished - Dec 2020

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