An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

Safina, K. R.; Kotliar, D. A.; Curtis, M.; Good, J. D.; weng, c.; David, S.; Raychaudhuri, S.; Kreso, A.; Trowbridge, J.; Sankaran, V. G.; van Galen, P.

doi:10.1101/2025.09.01.673389

bioRxiv · 10.1101/2025.09.01.673389

An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans

Safina, K. R.·Kotliar, D. A.·Curtis, M.·Good, J. D.·weng, c.·David, S.·Raychaudhuri, S.·Kreso, A.·Trowbridge, J.·Sankaran, V. G.·van Galen, P.

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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.

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Safina, K. R., Kotliar, D. A., Curtis, M., Good, J. D., weng, c., David, S., Raychaudhuri, S., Kreso, A., Trowbridge, J., Sankaran, V. G., van Galen, P.. 2025-09-04. An Inflammatory and Quiescent HSC Subpopulation Expands with Age in Humans. https://doi.org/10.1101/2025.09.01.673389

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