DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
17 04 2023
Historique:
received: 08 07 2021
accepted: 03 03 2023
medline: 19 4 2023
entrez: 17 4 2023
pubmed: 18 4 2023
Statut: epublish

Résumé

Ageing is associated with changes in the cellular composition of the immune system. During ageing, hematopoietic stem and progenitor cells (HSPCs) that produce immune cells are thought to decline in their regenerative capacity. However, HSPC function has been mostly assessed using transplantation assays, and it remains unclear how HSPCs age in the native bone marrow niche. To address this issue, we present an in situ single cell lineage tracing technology to quantify the clonal composition and cell production of single cells in their native niche. Our results demonstrate that a pool of HSPCs with unequal output maintains myelopoiesis through overlapping waves of cell production throughout adult life. During ageing, the increased frequency of myeloid cells is explained by greater numbers of HSPCs contributing to myelopoiesis rather than the increased myeloid output of individual HSPCs. Strikingly, the myeloid output of HSPCs remains constant over time despite accumulating significant transcriptomic changes throughout adulthood. Together, these results show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs in their native microenvironment do not functionally decline in their regenerative capacity.

Identifiants

pubmed: 37069150
doi: 10.1038/s41467-023-37167-8
pii: 10.1038/s41467-023-37167-8
pmc: PMC10110593
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2184

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Jos Urbanus (J)

Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Jason Cosgrove (J)

Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France.

Joost B Beltman (JB)

Division of Drug Discovery & Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.

Yuval Elhanati (Y)

Memorial Sloan Kettering Cancer Center, New York, USA.

Rafael A Moral (RA)

Department of Mathematics and Statistics, Maynooth University, Maynooth, Ireland.

Cecile Conrad (C)

Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France.

Jeroen W van Heijst (JW)

Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Emilie Tubeuf (E)

Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France.

Arno Velds (A)

Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Lianne Kok (L)

Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Candice Merle (C)

Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France.

Jens P Magnusson (JP)

Department of Bioengineering, Stanford University, Stanford, USA.

Léa Guyonnet (L)

Cytometry Platform, Institut Curie, 75005, Paris, France.

Jonas Frisén (J)

Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.

Silvia Fre (S)

Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France.

Aleksandra M Walczak (AM)

Laboratoire de Physique de l'École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, Paris, France.

Thierry Mora (T)

Laboratoire de Physique de l'École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, Paris, France.

Heinz Jacobs (H)

Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Ton N Schumacher (TN)

Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands. t.schumacher@nki.nl.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. t.schumacher@nki.nl.

Leïla Perié (L)

Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France. leila.perie@curie.fr.

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