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.

Brigham and Women\'s HospitalBrigham and Women\'s Hospital · biorxiv

Paper

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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Research summary

The paper identifies a gene expression program linking inflammatory pathway activation and quiescence in aging hematopoietic stem cells. This research is relevant as it explores the underlying mechanisms of aging at the cellular level, potentially informing strategies for interventions that target the root causes of aging.

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