An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

Ksenia R. Safina; Basit Salik; Dylan Kotliar; Michelle L. Curtis; Jonathan Good; Chen Weng; Shawn David; Soumya Raychaudhuri; Antonia Kreso; Jennifer J. Trowbridge; Vijay G. Sankaran; Peter van Galen

doi:10.1186/s13059-026-03936-z

Cell BiologyGenome biologyJan 16, 2026

Peer-reviewed journal article

An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

Ksenia R. Safina iD, Basit Salik iD, Dylan Kotliar iD, Michelle L. Curtis iD, Jonathan Good iD, Chen Weng iD, Shawn David, Soumya Raychaudhuri iD, Antonia Kreso iD, Jennifer J. Trowbridge iD, Vijay G. Sankaran iD, Peter van Galen iD

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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/NF{kappa}B, 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.