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

Jos Urbanus, Jason Cosgrove, Joost B. Beltman, Yuval Elhanati, Rafael A. Moral, Cecile Conrad, Jeroen W. Heijst, Emilie Tubeuf, Arno Velds, Lianne Kok, Candice Merle, Jens P. Magnusson, Léa Guyonnet, Jonas Frisén, Silvia Fre, Aleksandra M. Walczak, Thierry Mora, Heinz Jacobs, Ton N. Schumacher () and Leïla Perié ()
Additional contact information
Jos Urbanus: Oncode Institute, The Netherlands Cancer Institute
Jason Cosgrove: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie
Joost B. Beltman: Leiden Academic Centre for Drug Research, Leiden University
Yuval Elhanati: Memorial Sloan Kettering Cancer Center
Rafael A. Moral: Maynooth University
Cecile Conrad: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie
Jeroen W. Heijst: Oncode Institute, The Netherlands Cancer Institute
Emilie Tubeuf: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie
Arno Velds: Oncode Institute, The Netherlands Cancer Institute
Lianne Kok: Oncode Institute, The Netherlands Cancer Institute
Candice Merle: PSL Research University, INSERM U934
Jens P. Magnusson: Stanford University
Léa Guyonnet: Institut Curie
Jonas Frisén: Karolinska Institute
Silvia Fre: PSL Research University, INSERM U934
Aleksandra M. Walczak: Laboratoire de Physique de l’École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris
Thierry Mora: Laboratoire de Physique de l’École Normale Supérieure (PSL University), CNRS, Sorbonne Université, and Université de Paris
Heinz Jacobs: The Netherlands Cancer Institute
Ton N. Schumacher: Oncode Institute, The Netherlands Cancer Institute
Leïla Perié: Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37167-8

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