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An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

2025/09/04 by Ksenia R. Safina, Dylan Kotliar, Michelle Curtis +8 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · Immunology and Microbiology · #Single-cell and spatial transcriptomics #Hematopoietic Stem Cell Transplantation #Immune cells in cancer

paper · pdf · doi:10.1101/2025.09.01.673389

Abstract

Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map revealed previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single gene expression program. This program dominates an inflammatory HSC subpopulation that increases with age, highlighting a potential target for further experimental studies and anti-aging interventions.

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