{
  "abstract": ", but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation-recovery 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada",
    "Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada",
    "MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK",
    "NIHR Oxford Biomedical Research Centre, Oxford, UK",
    "Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada",
    "Ontario Institute for Cancer Research, Toronto, Ontario, Canada",
    "Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA",
    "Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, NewYork, NY, USA",
    "Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA",
    "Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA",
    "Department of Hematology, Centro Hospitalar Universitário de São João, Porto, Portugal",
    "Faculty of Medicine, University of Porto, Porto, Portugal",
    "Instituto Nacional de Investigação Biomédica, University of Porto, Porto, Portugal",
    "Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal",
    "Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, British Columbia, Canada",
    "Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada",
    "Division of Pulmonary and Critical Care Medicine, Weill Cornell Graduate School, NewYork, NY, USA",
    "Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Computer Science, University of Toronto, Toronto, Ontario, Canada",
    "Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada",
    "Vector Institute, Toronto, Ontario, Canada",
    "Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada",
    "The Jackson Laboratory, Bar Harbor, ME, USA",
    "Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA",
    "Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK",
    "Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK",
    "Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. stephanie.xie@uhn.ca",
    "Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. stephanie.xie@uhn.ca"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 37,
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        0,
        1
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      "name": "Andy G.X. Zeng",
      "orcid": "0000-0002-3223-6400"
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      "name": "Murtaza S. Nagree",
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      "name": "Niels Asger Jakobsen",
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      "name": "Sayyam Shah",
      "orcid": "0009-0005-1064-3223"
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      "name": "Angelica Varesi",
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        1
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      "name": "Jasmine Ryu Won Kang",
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      "name": "Alex Murison",
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      "name": "Jin‐Gyu Cheong",
      "orcid": "0000-0002-6190-0411"
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      "name": "Sven Turkalj",
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      "name": "Xuan Zhang",
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      "name": "Felix A. Radtke",
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      "name": "Tsega‐Ab Abera"
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      "name": "Isabel N.X. Lim",
      "orcid": "0000-0002-0716-1566"
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    {
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        1
      ],
      "name": "Liqing Jin",
      "orcid": "0009-0009-9639-4836"
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        10,
        11,
        12,
        13
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      "name": "Joana Araújo",
      "orcid": "0000-0001-6220-1498"
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        1
      ],
      "name": "Alicia G. Aguilar-Navarro",
      "orcid": "0000-0001-6409-0613"
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        1
      ],
      "name": "Darrien Parris",
      "orcid": "0000-0001-7725-6213"
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    {
      "affs": [
        1
      ],
      "name": "Jessica McLeod"
    },
    {
      "affs": [
        1
      ],
      "name": "Hyerin Kim",
      "orcid": "0000-0002-4315-6078"
    },
    {
      "affs": [
        1
      ],
      "name": "Ho Seok Lee",
      "orcid": "0009-0009-5892-543X"
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    {
      "affs": [
        14,
        15
      ],
      "name": "Lin Zhang"
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    {
      "affs": [
        1
      ],
      "name": "Mason Boulanger"
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    {
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        0,
        5
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      "name": "Elyssa Bader"
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    {
      "affs": [
        5
      ],
      "name": "Elias Gbeha"
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    {
      "affs": [
        16
      ],
      "name": "Christopher N. Parkhurst",
      "orcid": "0000-0003-1725-3939"
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    {
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        17,
        1
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      "name": "Elvin Wagenblast",
      "orcid": "0000-0002-0709-2759"
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    {
      "affs": [
        1
      ],
      "name": "Eugenia Flores Figueroa",
      "orcid": "0000-0002-7453-1125"
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    {
      "affs": [
        18,
        19,
        15,
        20
      ],
      "name": "Bo Wang",
      "orcid": "0000-0002-9620-3413"
    },
    {
      "affs": [
        21,
        1
      ],
      "name": "Gregory W. Schwartz",
      "orcid": "0000-0003-4003-3045"
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    {
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        22
      ],
      "name": "Leonard D. Shultz",
      "orcid": "0000-0002-4868-1031"
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        6
      ],
      "name": "Anna S. Nam",
      "orcid": "0000-0003-4192-8916"
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      "name": "H. Leighton Grimes",
      "orcid": "0000-0001-8162-6758"
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    {
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        6,
        7
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      "name": "Steven Zvi Josefowicz",
      "orcid": "0000-0001-7453-779X"
    },
    {
      "affs": [
        24
      ],
      "name": "Philip Awadalla",
      "orcid": "0000-0001-9946-6393"
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    {
      "affs": [
        25,
        2,
        3
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      "name": "Paresh Vyas",
      "orcid": "0000-0003-3931-0914"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "John Edgar Dick",
      "orcid": "0000-0002-9527-8317"
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    {
      "affs": [
        26,
        27
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      "name": "Stephanie Zhi-Juan Xie",
      "orcid": "0000-0002-0284-494X"
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  "bibtex": "https://research.draconitic.com/paper/e1807krrxec89.bib",
  "cited_by": 36,
  "doi": "10.1038/s41586-026-10522-7",
  "fulltext_url": null,
  "id": "e1807krrxec89",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10522-7",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Hematopoietic Stem Cell Transplantation"
    ]
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  "openalex": "W7162495308",
  "pdf_url": null,
  "pmcid": "PMC13345971",
  "pmid": "42203882",
  "published": "2026-05-27",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/e1807krrxec89.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
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      "url": "https://doi.org/10.1038/s41586-026-10522-7"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Hematopoietic Stem Cell Transplantation",
      "subfield": "general"
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  ],
  "title": "Human haematopoietic stem cells remember inflammatory stress",
  "title_text": "Human haematopoietic stem cells remember inflammatory stress",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:13Z",
  "url": "https://research.draconitic.com/paper/e1807krrxec89",
  "venue": "Nature",
  "versions": []
}