An inflammatory and quiescent HSC subpopulation expands with age in humans
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.
Authors
- Antonia Kreso (ORCID: https://orcid.org/0000-0003-0632-958X)
- Basit Salik (ORCID: https://orcid.org/0000-0002-9300-8014)
- Michelle L. Curtis (ORCID: https://orcid.org/0000-0002-6843-4839)
- Jonathan Good (ORCID: https://orcid.org/0000-0002-4086-5709)
- Jennifer J. Trowbridge (ORCID: https://orcid.org/0000-0002-7636-9504)
- Peter M. van Galen
- Dylan Kotliar (ORCID: https://orcid.org/0000-0002-7968-645X)
- Ksenia R. Safina (ORCID: https://orcid.org/0000-0002-5126-9953)
- Shawn David
- Chen Weng
- Soumya Raychaudhuri
- Vijay G. Sankaran
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Jackson Laboratory (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Whitehead Institute for Biomedical Research (US)
- Harvard Stem Cell Institute (US)
- University of Maine (US)
Publication Details
- Journal
- Genome biology
- Published
- 2026-01-16
- DOI
- https://doi.org/10.1186/s13059-026-03936-z
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00