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

Amann-Zalcenstein, D, Tian, L, Schreuder, J, Tomei, S, Lin, DS, Fairfax, KA ORCID: 0000-0002-8394-137X, 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 and Naik, SH 2020 , 'A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics' , Nature Immunology, vol. 21, no. 12 , pp. 1574-1584 , doi: 10.1038/s41590-020-0799-x.

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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, 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
Journal or Publication Title: Nature Immunology
Publisher: Nature Publishing Group
ISSN: 1529-2908
DOI / ID Number: 10.1038/s41590-020-0799-x
Copyright Information:

Copyright 2020 Nature Publishing Group

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