{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:34Z","timestamp":1790794534238,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Hematopoietic stem cells (HSCs) sustain lifelong hematopoiesis as their progeny differentiate into all blood cell lineages. Homeostatic HSCs are mostly quiescent and only rarely divide, however their proliferation and differentiation rates can be modulated by external factors. Acute and chronic infections from a wide range of pathogens are known to challenge HSCs at the population level, being forced to respond to inflammation-mediated organismal demand to replenish the myeloid cell pool. However, less is known about the degree of heterogeneity in the HSCs' response to inflammation at the single cell level. Here, using a natural murine malaria model and an NHS-ester biotin dilution assay we identify two subsets of HSCs, BiotinLo and BiotinHi, with distinct proliferation kinetics. Using combined functional, single-cell transcriptomics and phenotypic analyses, we uncover that BiotinHi HSCs remain highly functional despite expressing strong interferon response signatures. These resilient HSCs are more poised to enter cell cycle than control HSCs, but do not divide. They maintain less active mitochondria and express higher levels of CD74 and MHC-II. Additionally, they express higher levels of integrin \u03b22\/CD18, which suggest they may have specific interactions with the bone marrow microenvironment. Similar patterns of NHS-ester biotin dilution were elicited by LPS and poly (I:C) challenges. These findings highlight previously unmeasured heterogeneity in the response of HSCs to acute infection-induced inflammation and demonstrate that a likely reserve pool of HSCs remains highly functional during Plasmodium infection not because cells are shielded, but because they maintain a stemness associated metabolic profile despite effectively sensing inflammation.<\/jats:p>","DOI":"10.1182\/blood.2025032368","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:13:45Z","timestamp":1788974025000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Rare Hematopoietic Stem Cells resilient to infection-induced stress sense yet withstand inflammation"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0569-5409","authenticated-orcid":false,"given":"Christiana","family":"Georgiou","sequence":"first","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3078-3785","authenticated-orcid":false,"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4241-3107","authenticated-orcid":false,"given":"Federica","family":"Bruno","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cera","family":"Mai","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-3535","authenticated-orcid":false,"given":"Floriane Simonne","family":"Tissot","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Fan","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gonzalez Anton","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Birch","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-2330","authenticated-orcid":false,"given":"Debangana","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Northeastern University, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J","family":"Kinston","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-6326","authenticated-orcid":false,"given":"Shirom","family":"Chabra","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lia","family":"Sergi","sequence":"additional","affiliation":[{"name":"UCLouvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-3590","authenticated-orcid":false,"given":"Nick","family":"van Gastel","sequence":"additional","affiliation":[{"name":"UCLouvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-3311","authenticated-orcid":false,"given":"Ilaria","family":"Malanchi","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0865-7333","authenticated-orcid":false,"given":"Nicola K","family":"Wilson","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken R.","family":"Duffy","sequence":"additional","affiliation":[{"name":"Northeastern University, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-1329","authenticated-orcid":false,"given":"Constandina","family":"Pospori","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Blagborough","sequence":"additional","affiliation":[{"name":"Cambridge University, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6302-5705","authenticated-orcid":false,"given":"Berthold","family":"Gottgens","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-1257","authenticated-orcid":false,"given":"Tiago C.","family":"Luis","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-4207","authenticated-orcid":false,"given":"Cristina","family":"Lo Celso","sequence":"additional","affiliation":[{"name":"Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2026,9,30]]},"container-title":["Blood Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025032368\/2588226\/blood.2025032368.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2025032368\/2588226\/blood.2025032368.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:06:22Z","timestamp":1790791582000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2025032368\/570868\/Rare-Hematopoietic-Stem-Cells-resilient-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2025032368","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"blood.2025032368"}}