Journal article

A new lymphoid-primed progenitor marked byDach1downregulation 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 Ng Show all

Nature Immunology | NATURE RESEARCH | Published : 2020

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 wi..

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Grants

Awarded by National Health & Medical Research Council


Funding Acknowledgements

We thank the WEHI flow cytometry facility, the Single Cell Open Research Endeavour, S. Wilcox for genomics support and Animal Bioservices for animal husbandry. This work was supported by the National Health & Medical Research Council, with fellowships to S.H.N. (0516782), J.E.B (0637403), C.d.G (1035229), S.L.N. (1155342) and W.S.A (1058344); project grants (1062820, 1124812, 1085765, 1060179, 1122783); a program grant (1113577), the Australian Research Council's special initiative Stem Cells Australia, an Australian Cancer Research Fund, Victorian State Government Infrastructure Support, Australian Government NHMRC IRIIS and CSL Limited.