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

journal contribution
posted on 2023-05-20, 19:44 authored by Amann-Zalcenstein, D, Tian, L, Schreuder, J, Tomei, S, Lin, DS, Kirsten FairfaxKirsten Fairfax, 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
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.

History

Publication title

Nature Immunology

Volume

21

Issue

12

Pagination

1574-1584

ISSN

1529-2908

Department/School

Menzies Institute for Medical Research

Publisher

Nature Publishing Group

Place of publication

345 Park Ave South, New York, USA, Ny, 10010-1707

Rights statement

Copyright 2020 Nature Publishing Group

Repository Status

  • Restricted

Socio-economic Objectives

Diagnosis of human diseases and conditions

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