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

Citation

Amann-Zalcenstein, D and Tian, L 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, A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics, Nature Immunology, 21, (12) pp. 1574-1584. ISSN 1529-2908 (2020) [Refereed Article]

Copyright Statement

Copyright 2020 Nature Publishing Group

DOI: doi: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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
ID Code:142014
Year Published:2020
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-12-08
Last Modified:2021-02-16
Downloads:0

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