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Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis\n                    <jats:sup>1\u20139<\/jats:sup>\n                    , but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation\u2013recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were identified with one, termed HSC inflammatory memory (HSC-iM), retaining a molecular memory of previous inflammatory treatments. The HSC-iM subset exhibited quiescence and restrained haematopoietic output. Molecularly, the HSC-iM program was enriched in HSCs from adult and paediatric samples across conditions ranging from COVID-19 recovery, sickle cell disease, ageing and clonal haematopoiesis, establishing both the validity of our xenograft models and the physiological relevance of HSC-iM. Clonal haematopoiesis mutations in HSC-iM attenuated the effects of inflammatory stress by promoting HSC activation and differentiation. Moreover, transmission of the pro-inflammatory HSC-iM transcriptional program to differentiated immune progeny was demonstrated in xenograft and physiological settings. Finally, HSC-iM program enrichment in circulating blood cells was associated with a heightened risk score for all-cause mortality in population cohort analyses, underscoring the clinical relevance of this newly identified HSC subset in characterizing heterogeneous health outcomes across a lifetime.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10522-7","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:01:43Z","timestamp":1779894103000},"page":"458-467","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Human haematopoietic stem cells remember inflammatory stress"],"prefix":"10.1038","volume":"655","author":[{"given":"Andy G. 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