Age-associated imbalance in immune cell regeneration varies across individuals and arises from a distinct subset of stem cells.
aging
clonal tracking
hematopoietic stem cells
lineage bias
myelopoiesis
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
24
01
2024
accepted:
23
09
2024
medline:
24
10
2024
pubmed:
24
10
2024
entrez:
24
10
2024
Statut:
aheadofprint
Résumé
The age-associated decline in immunity manifests as imbalanced adaptive and innate immune cells, which originate from the aging of the stem cells that sustain their regeneration. Aging variation across individuals is well recognized, but its mechanism remains unclear. Here, we used high-throughput single-cell technologies to compare mice of the same chronological age that exhibited early or delayed immune aging phenotypes. We found that some hematopoietic stem cells (HSCs) in early aging mice upregulated genes related to aging, myeloid differentiation, and stem cell proliferation. Delayed aging was instead associated with genes involved in stem cell regulation and the response to external signals. These molecular changes align with shifts in HSC function. We found that the lineage biases of 30% to 40% of the HSC clones shifted with age. Moreover, their lineage biases shifted in opposite directions in mice exhibiting an early or delayed aging phenotype. In early aging mice, the HSC lineage bias shifted toward the myeloid lineage, driving the aging phenotype. In delayed aging mice, HSC lineage bias shifted toward the lymphoid lineage, effectively counteracting aging progression. Furthermore, the anti-aging HSC clones did not increase lymphoid production but instead decreased myeloid production. Additionally, we systematically quantified the frequency of various changes in HSC differentiation and their roles in driving the immune aging phenotype. Taken together, our findings suggest that temporal variation in the aging of immune cell regeneration among individuals primarily arises from differences in the myelopoiesis of a distinct subset of HSCs. Therefore, interventions to delay aging may be possible by targeting a subset of stem cells.
Identifiants
pubmed: 39443746
doi: 10.1038/s41423-024-01225-y
pii: 10.1038/s41423-024-01225-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01HL138225
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R35HL150826
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : 1F31HL149278-01A1
Organisme : Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)
ID : LLS-1370-20
Organisme : California Institute for Regenerative Medicine (CIRM)
ID : EDUC4-12756
Informations de copyright
© 2024. The Author(s).
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