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Identification of a human hematopoietic stem cell subset that retains memory of inflammatory stress [XenoProg_Myeloid]

ABSTRACT: Hematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long blood production. Inflammation activates many blood cell types, driving aging and malignancy. To understand HSC adaptation to inflammation, we performed single cell multi-omics on human HSC in xenograft inflammation-recovery models. Two transcriptionally and epigenetically distinct HSC subsets expressing canonical HSC programs were identified. Only one showed sustained transcriptional and epigenetic changes after recovery from inflammatory treatments. This HSC inflammatory memory (HSC-iM) program is enriched in memory T cells and HSC from recovered COVID-19 patients. Importantly, HSC-iM accumulates with age and in clonal hematopoiesis. Overall, heritable molecular alterations in a subset of human HSCs, an adaptation to long-term inflammatory stress, may predispose to heightened age related risk of blood cancer and infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE318050 | GEO | 2026/03/09

REPOSITORIES: GEO

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