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

Autor: Urbanus J; Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Cosgrove J; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France., Beltman JB; Division of Drug Discovery & Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands., Elhanati Y; Memorial Sloan Kettering Cancer Center, New York, USA., Moral RA; Department of Mathematics and Statistics, Maynooth University, Maynooth, Ireland., Conrad C; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France., van Heijst JW; Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Tubeuf E; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France., Velds A; Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Kok L; Division of Molecular Oncology & Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Merle C; Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France., Magnusson JP; Department of Bioengineering, Stanford University, Stanford, USA., Guyonnet L; Cytometry Platform, Institut Curie, 75005, Paris, France., Frisén J; Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden., Fre S; Institut Curie, Laboratory of Genetics and Developmental Biology, PSL Research University, INSERM U934, CNRS UMR3215, Paris, France., Walczak AM; Laboratoire de Physique de l'École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, Paris, France., Mora T; Laboratoire de Physique de l'École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris, Paris, France., Jacobs H; Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., 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., Perié L; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, 75005, Paris, France. leila.perie@curie.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 17; Vol. 14 (1), pp. 2184. Date of Electronic Publication: 2023 Apr 17.
DOI: 10.1038/s41467-023-37167-8
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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