DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2023

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

Jos Urbanus
Jason Cosgrove
  • Fonction : Auteur
Joost Beltman
Yuval Elhanati
  • Fonction : Auteur
Rafael Moral
  • Fonction : Auteur
Cecile Conrad
  • Fonction : Auteur
Jeroen van Heijst
  • Fonction : Auteur
Emilie Tubeuf
  • Fonction : Auteur
Arno Velds
Lianne Kok
  • Fonction : Auteur
Candice Merle
  • Fonction : Auteur
Jens Magnusson
Léa Guyonnet
  • Fonction : Auteur
Jonas Frisén
Silvia Fre
  • Fonction : Auteur
Heinz Jacobs
Ton Schumacher
Leïla Perié

Résumé

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.

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hal-04252234 , version 1 (20-10-2023)

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Jos Urbanus, Jason Cosgrove, Joost Beltman, Yuval Elhanati, Rafael Moral, et al.. DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age. Nature Communications, 2023, 14 (1), pp.2184. ⟨10.1038/s41467-023-37167-8⟩. ⟨hal-04252234⟩
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