An inflammatory and quiescent HSC subpopulation expands with age in humans

TL;DR

The study finds an inflammatory and inactive stem cell subgroup in blood that grows with age in humans, offering a new target for anti-aging research.

Contribution

A unified gene expression map of aging hematopoietic stem cells reveals a novel inflammatory and quiescent subpopulation linked to aging.

Findings

Integrated single-cell datasets show HSC heterogeneity and age-related changes.

An inflammatory and quiescent HSC subpopulation expands with age.

This subpopulation is marked by TNF/NFκB and AP-1 pathway activation.

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 reveals 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.

The online version contains supplementary material available at 10.1186/s13059-026-03936-z.

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