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. Ng; Shalin H. Naik

doi:10.1038/s41590-020-0799-x

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

Australian Centre for Blood Diseases

Research output: Contribution to journal › Article › Research › peer-review

24 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. 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.

Original language	English
Pages (from-to)	1574-1584
Number of pages	11
Journal	Nature Immunology
Volume	21
Issue number	12
DOIs	https://doi.org/10.1038/s41590-020-0799-x
Publication status	Published - Dec 2020

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10.1038/s41590-020-0799-x

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Amann-Zalcenstein, D., Tian, L., Schreuder, J., Tomei, S., Lin, D. S., Fairfax, K. A., Bolden, J. E., McKenzie, M. D., Jarratt, A., Hilton, A., Jackson, J. T., Di Rago, L., McCormack, M. P., de Graaf, C. A., Stonehouse, O., Taoudi, S., Alexander, W. S., Nutt, S. L., Ritchie, M. E., ... Naik, S. H. (2020). A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics. Nature Immunology, 21(12), 1574-1584. https://doi.org/10.1038/s41590-020-0799-x

@article{8897aa6c6339449e87d7f791ef661ac3,

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

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 {\textquoteleft}lymphoid-primed progenitors{\textquoteright} (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.",

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

year = "2020",

month = dec,

doi = "10.1038/s41590-020-0799-x",

language = "English",

volume = "21",

pages = "1574--1584",

journal = "Nature Immunology",

issn = "1529-2908",

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Amann-Zalcenstein, D, Tian, L, Schreuder, J, Tomei, S, Lin, DS, Fairfax, KA, 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 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. https://doi.org/10.1038/s41590-020-0799-x

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T1 - A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics

AU - Amann-Zalcenstein, Daniela

AU - Tian, Luyi

AU - Schreuder, Jaring

AU - Tomei, Sara

AU - Lin, Dawn S.

AU - Fairfax, Kirsten A.

AU - Bolden, Jessica E.

AU - McKenzie, Mark D.

AU - Jarratt, Andrew

AU - Hilton, Adrienne

AU - Jackson, Jacob T.

AU - Di Rago, Ladina

AU - McCormack, Matthew P.

AU - de Graaf, Carolyn A.

AU - Stonehouse, Olivia

AU - Taoudi, Samir

AU - Alexander, Warren S.

AU - Nutt, Stephen L.

AU - Ritchie, Matthew E.

AU - Ng, Ashley P.

AU - Naik, Shalin H.

PY - 2020/12

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N2 - 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.

AB - 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.

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SP - 1574

EP - 1584

JO - Nature Immunology

JF - Nature Immunology

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

Abstract

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The role of the homeobox transcription factor Hhex in haematopoiesis and leukaemia

Development of a system to detect disease outbreaks in semi-isolated communities using automated monitoring of electronic data

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

Abstract

Access to Document

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The role of the homeobox transcription factor Hhex in haematopoiesis and leukaemia

Development of a system to detect disease outbreaks in semi-isolated communities using automated monitoring of electronic data

Cite this