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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Vydáno v:	Nature communications Ročník 14; číslo 1; s. 2184 - 14
Hlavní autoři:	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:	angličtina
Vydáno:	London Nature Publishing Group UK 17.04.2023 Nature Publishing Group Nature Portfolio
Témata:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-023-37167-8