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

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 as...

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Published in:bioRxiv
Main Authors: Urbanus, Jos, Cosgrove, Jason, Beltman, Joost, Elhanati, Yuval, De Andrade Moral, Rafael, Conrad, Cecile, Jeroen Van Heijst, Tubeuf, Emilie, Velds, Arno, Kok, Lianne, Merle, Candice, Magnusson, Jens P, Frisen, Jonas, Fre, Silvia, Walczak, Aleksandra, Mora, Thierry, Jacobs, Heinz, Shumacher, Ton, Perie, Leila
Format: Paper Publication
Language:English
Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 09.12.2022
Cold Spring Harbor Laboratory
Edition:1.1
Subjects:
Aging
Bone marrow
Cell lineage
Hematopoietic stem cells
Immune system
Immunology
Microenvironments
Myeloid cells
Myelopoiesis
Progenitor cells
Transcriptomics
Transplantation
ISSN:2692-8205, 2692-8205
Online Access:Get full text
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Summary: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 developed a novel 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 increased myeloid output of individual HSPCs. Strikingly, the myeloid output of HSPCs remained 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.Competing Interest StatementThe authors have declared no competing interest.
Bibliography:SourceType-Working Papers-1
ObjectType-Working Paper/Pre-Print-1
content type line 50
Competing Interest Statement: The authors have declared no competing interest.
ISSN:2692-8205
2692-8205
DOI:10.1101/2022.12.06.519273