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


Authors: Urbanus, J.; Cosgrove, J.; Beltman, J. B.; Elhanati, Y.; Moral, R. A.; Conrad, C.; van Heijst, J. W.; Tubeuf, E.; Velds, A.; Kok, L.; Merle, C.; Magnusson, J. P.; Guyonnet, L.; Frisén, J.; Fre, S.; Walczak, A. M.; Mora, T.; Jacobs, H.; Schumacher, T. N.; Perié, L.
Article Title: DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age
Abstract: 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).
Keywords: adult; human tissue; aged; human cell; genetics; bone marrow cells; bone marrow; transplantation; cell lineage; hematopoietic stem cells; aging; bone marrow cell; microenvironment; hematopoietic stem cell; adulthood; myeloid cells; myelopoiesis; humans; human; article
Journal Title: Nature Communications
Volume: 14
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2023-04-17
Start Page: 2184
Language: English
DOI: 10.1038/s41467-023-37167-8
PUBMED: 37069150
PROVIDER: scopus
PMCID: PMC10110593
DOI/URL:
Notes: Article -- Export Date: 1 May 2023 -- Source: Scopus
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