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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Vydané v:Nature communications Ročník 14; číslo 1; s. 2184 - 14
Hlavní autori: Urbanus, Jos, Cosgrove, Jason, Beltman, Joost B., Elhanati, Yuval, Moral, Rafael A., Conrad, Cecile, van Heijst, Jeroen W., Tubeuf, Emilie, Velds, Arno, Kok, Lianne, Merle, Candice, Magnusson, Jens P., Guyonnet, Léa, Frisén, Jonas, Fre, Silvia, Walczak, Aleksandra M., Mora, Thierry, Jacobs, Heinz, Schumacher, Ton N., Perié, Leïla
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 17.04.2023
Nature Publishing Group
Nature Portfolio
Predmet:
13
13/31
14
38
38/77
42
45
49
49/23
49/91
59
631/250/232
631/532/2118/1542
631/532/7
64
64/110
96
Adult
Aged
Aging
Bone Marrow
Bone Marrow Cells
Cell lineage
Cells (biology)
Cellular Biology
Composition
Drag
Hematopoietic Stem Cells
Humanities and Social Sciences
Humans
Immune system
Life Sciences
Microenvironments
multidisciplinary
Myeloid Cells
Myelopoiesis
Myelopoiesis - genetics
Progenitor cells
Science
Science (multidisciplinary)
Subcellular Processes
Tracing
Transcriptomics
Transplantation
barcoding
ageing
hematopoiesis
single cell
clonality
lineage tracing
ISSN:2041-1723, 2041-1723
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Shrnutí: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. Using in situ single cell lineage tracing technology DRAG, we show that, unlike emergency myelopoiesis post-transplantation, aged HSPCs do not functionally decline in the number of myeloid cells that they produce.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-37167-8