{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:28Z","timestamp":1789450408632,"version":"build-2803163510"},"reference-count":106,"publisher":"Rockefeller University Press","issue":"2","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TIGET Core Grant B2"],"award-info":[{"award-number":["TIGET Core Grant B2"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TIGET Core Grant E5"],"award-info":[{"award-number":["TIGET Core Grant E5"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003197","name":"Italian Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2019-12369499"],"award-info":[{"award-number":["GR-2019-12369499"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000854","name":"Human Frontier Science Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011207","name":"New York Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"AIRC","doi-asserted-by":"publisher","award":["MFAG 2019\u2013PI ID.23321"],"award-info":[{"award-number":["MFAG 2019\u2013PI ID.23321"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101003186"],"award-info":[{"award-number":["101003186"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union - NextGeneration EU","award":["D43C22003100007"],"award-info":[{"award-number":["D43C22003100007"]}]},{"name":"European Union - NextGeneration EU","award":["PE000015"],"award-info":[{"award-number":["PE000015"]}]},{"DOI":"10.13039\/100009812","name":"Princess Margaret Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009812","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Allan Slaight Breakthrough Fund"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:p>Hematopoietic stem\/progenitor cells (HSPC) aging has long been associated with myeloid skewing, reduced clonal output, and impaired regenerative capacity, but quantitative immunophenotypic and functional analysis across the human lifespan has been lacking. Here, we provide a comprehensive phenotypic, transcriptional, and functional dissection of human hematopoiesis from youth to advanced age. Although primitive hematopoietic stem cell (HSC) numbers were stable during aging, overall cellularity declined, especially for erythroid and lymphoid lineages. HSPCs from older individuals exhibited repopulating frequencies comparable with those from younger donors in both primary and secondary xenografts; however, aged HSCs displayed impaired differentiation, chromatin and cell cycle dysregulation, and poor tolerance to activation-induced proliferative stress, resulting in DNA damage and senescence-like features after xenotransplantation. Importantly, imposing proliferative stress on young human HSPCs in vivo recapitulated key aging-associated phenotypic and functional declines. Together, our findings identify dysregulated activation responses as a defining feature of HSPC aging and establish proliferative stress\u2013based xenotransplantation models as powerful platforms for investigating age-related hematopoietic dysfunctions.<\/jats:p>","DOI":"10.1084\/jem.20251805","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T07:20:58Z","timestamp":1764919258000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2680-2222","authenticated-orcid":true,"given":"Emanuele","family":"Lettera","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-005X","authenticated-orcid":true,"given":"Luca","family":"Basso-Ricci","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6200-2868","authenticated-orcid":true,"given":"Edoardo","family":"Carsana","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7989-2520","authenticated-orcid":true,"given":"Kety","family":"Giannetti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-4413","authenticated-orcid":true,"given":"Teresa","family":"Tavella","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7028-6125","authenticated-orcid":true,"given":"Luca","family":"Seffin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-1497","authenticated-orcid":true,"given":"Giacomo","family":"Farina","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6118","authenticated-orcid":true,"given":"Nicol\u00f2","family":"Gualandi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2988-5387","authenticated-orcid":true,"given":"Pamela","family":"Quaranta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1414-0154","authenticated-orcid":true,"given":"Elena","family":"Lo Furno","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6506-6949","authenticated-orcid":true,"given":"Guido","family":"Pacini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9087-1293","authenticated-orcid":true,"given":"Lucrezia","family":"della Volpe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5013-6123","authenticated-orcid":true,"given":"Kerstin B.","family":"Kaufmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3786-4852","authenticated-orcid":true,"given":"Laura","family":"Garcia-Prat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-9042","authenticated-orcid":true,"given":"Raisa Jofra","family":"Hernandez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-4686","authenticated-orcid":true,"given":"Alex","family":"Murison","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-0613","authenticated-orcid":true,"given":"Alicia G.","family":"Aguilar-Navarro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Oncol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social 4 , Mexico City,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-004X","authenticated-orcid":true,"given":"Stefano","family":"Beretta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-2649","authenticated-orcid":true,"given":"Anastasia","family":"Conti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-1125","authenticated-orcid":true,"given":"Eugenia","family":"Flores-Figueroa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Oncol\u00f3gicas, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social 4 , Mexico City,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-2745","authenticated-orcid":true,"given":"Marco","family":"Ometti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039zxt351","id-type":"ROR","asserted-by":"publisher"}],"name":"IRCCS Ospedale San Raffaele 5 Department of Orthopedic Surgery and Traumatology, , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3587-3680","authenticated-orcid":true,"given":"Ivan","family":"Merelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5398-1717","authenticated-orcid":true,"given":"Alessandro","family":"Aiuti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele 2 , Milan,","place":["Italy"]},{"name":"Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute 6 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-494X","authenticated-orcid":true,"given":"Stephanie Z.","family":"Xie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03zayce58","id-type":"ROR","asserted-by":"publisher"}],"name":"University Health Network, Princess Margaret Cancer Centre 3 , Toronto,","place":["Canada"]},{"name":"University of Toronto 7 Department of Medical Biophysics, , Toronto,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-3809","authenticated-orcid":true,"given":"Serena","family":"Scala","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-8238","authenticated-orcid":true,"given":"Raffaella","family":"Di Micco","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036jn4298","id-type":"ROR","asserted-by":"publisher"}],"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele 1 , Milan,","place":["Italy"]},{"name":"University School of Advanced Studies IUSS 8 , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"2026060910070936700_bib1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.stemcr.2020.06.011","article-title":"Human aging alters the spatial organization between CD34+ hematopoietic cells and adipocytes in bone marrow","volume":"15","author":"Aguilar-Navarro","year":"2020","journal-title":"Stem Cell Rep."},{"key":"2026060910070936700_bib2","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.12688\/f1000research.10082.1","article-title":"Disambiguate: An open-source application for disambiguating two species in next generation sequencing data from grafted samples","volume":"5","author":"Ahdesm\u00e4ki","year":"2016","journal-title":"F1000Res."},{"key":"2026060910070936700_bib3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.79363","article-title":"Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution","volume":"12","author":"Ainciburu","year":"2023","journal-title":"Elife"},{"key":"2026060910070936700_bib4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41467-017-02376-5","article-title":"Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space","volume":"9","author":"Akinduro","year":"2018","journal-title":"Nat. Commun."},{"key":"2026060910070936700_bib5","doi-asserted-by":"publisher","first-page":"393","DOI":"10.3324\/haematol.2020.269670","article-title":"Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity","volume":"107","author":"Amoah","year":"2022","journal-title":"Haematologica"},{"key":"2026060910070936700_bib6","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm953","article-title":"Ex vivo expansion of human hematopoietic stem cells by direct delivery of the HOXB4 homeoprotein","volume":"9","author":"Amsellem","year":"2003","journal-title":"Nat. Med."},{"key":"2026060910070936700_bib7","doi-asserted-by":"publisher","first-page":"S40","DOI":"10.1016\/j.bbmt.2011.11.003","article-title":"From biology to clinical Practice: Aging and hematopoietic cell transplantation","volume":"18","author":"Artz","year":"2012","journal-title":"Biol. Blood Marrow Transpl."},{"key":"2026060910070936700_bib8","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.tcb.2022.12.001","article-title":"Clonal hematopoiesis and inflammation \u2013 the perpetual cycle","volume":"33","author":"Avagyan","year":"2023","journal-title":"Trends Cell Biol."},{"key":"2026060910070936700_bib9","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1002\/cyto.a.23148","article-title":"Multiparametric whole blood dissection: A one-shot comprehensive picture of the human hematopoietic system","volume":"91","author":"Basso-Ricci","year":"2017","journal-title":"Cytometry A"},{"key":"2026060910070936700_bib10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.stem.2013.01.017","article-title":"Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging","volume":"12","author":"Beerman","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib11","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.stem.2014.04.016","article-title":"Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle","volume":"15","author":"Beerman","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib12","doi-asserted-by":"publisher","first-page":"4100","DOI":"10.1038\/s41467-018-06442-4","article-title":"Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors","volume":"9","author":"Belluschi","year":"2018","journal-title":"Nat. Commun."},{"key":"2026060910070936700_bib13","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.cell.2016.10.022","article-title":"Hematopoietic stem cells count and remember self-renewal divisions","volume":"167","author":"Bernitz","year":"2016","journal-title":"Cell"},{"key":"2026060910070936700_bib14","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.stem.2022.06.012","article-title":"Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging","volume":"29","author":"Bogeska","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib15","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","article-title":"Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position","volume":"10","author":"Buenrostro","year":"2013","journal-title":"Nat. Methods"},{"key":"2026060910070936700_bib16","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2026060910070936700_bib17","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1182\/bloodadvances.2017009852","article-title":"Aging, hematopoiesis, and the myelodysplastic syndromes","volume":"1","author":"Chung","year":"2017","journal-title":"Blood Adv."},{"key":"2026060910070936700_bib18","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: Making it safe to play with knives","volume":"40","author":"Ciccia","year":"2010","journal-title":"Mol. Cell"},{"key":"2026060910070936700_bib19","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.chom.2020.05.014","article-title":"BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment","volume":"28","author":"Cirovic","year":"2020","journal-title":"Cell Host Microbe"},{"key":"2026060910070936700_bib20","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1182\/blood-2017-06-746412","article-title":"Aging of hematopoietic stem cells","volume":"131","author":"de Haan","year":"2018","journal-title":"Blood"},{"key":"2026060910070936700_bib21","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.stem.2020.01.017","article-title":"C\/EBP\u03b2-Dependent epigenetic memory induces trained immunity in hematopoietic stem cells","volume":"26","author":"de Laval","year":"2020","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib22","doi-asserted-by":"publisher","first-page":"101823","DOI":"10.1016\/j.xcrm.2024.101823","article-title":"A p38 MAPK-ROS axis fuels proliferation stress and DNA damage during CRISPR-Cas9 gene editing in hematopoietic stem and progenitor cells","volume":"5","author":"della Volpe","year":"2024","journal-title":"Cell Rep Med"},{"key":"2026060910070936700_bib23","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.stem.2012.01.006","article-title":"Hematopoiesis: A human perspective","volume":"10","author":"Doulatov","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib24","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1007\/s00277-023-05226-1","article-title":"Allogeneic hematopoietic stem cell transplantation remains a feasible approach for elderly with acute myeloid leukemia: A 10-year experience","volume":"102","author":"Duda","year":"2023","journal-title":"Ann. Hematol."},{"key":"2026060910070936700_bib25","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.stem.2007.05.015","article-title":"Long-term propagation of distinct hematopoietic differentiation programs in vivo","volume":"1","author":"Dykstra","year":"2007","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib106","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Ombibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2026060910070936700_bib107","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"ENCODE Project Consortium","year":"2012","journal-title":"Nature"},{"key":"2026060910070936700_bib26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nature13619","article-title":"Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells","volume":"512","author":"Flach","year":"2014","journal-title":"Nature"},{"key":"2026060910070936700_bib27","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1038\/s41591-025-03716-5","article-title":"A reference model of circulating hematopoietic stem cells across the lifespan with applications to diagnostics","volume":"31","author":"Furer","year":"2025","journal-title":"Nat. Med."},{"key":"2026060910070936700_bib28","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1016\/j.stem.2021.07.003","article-title":"TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate","volume":"28","author":"Garc\u00eda-Prat","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib29","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/1471-2105-11-367","article-title":"A flexible R package for nonnegative matrix factorization","volume":"11","author":"Gaujoux","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2026060910070936700_bib30","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"2026060910070936700_bib31","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1182\/blood.2022017174","article-title":"Aging alters the cell cycle control and mitogenic signaling responses of human hematopoietic stem cells","volume":"141","author":"Hammond","year":"2023","journal-title":"Blood"},{"key":"2026060910070936700_bib32","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"2026060910070936700_bib33","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"2026060910070936700_bib34","doi-asserted-by":"publisher","first-page":"21713","DOI":"10.1073\/pnas.1005486107","article-title":"Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis","volume":"107","author":"Henry","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","article-title":"ELDA: Extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays","volume":"347","author":"Hu","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"2026060910070936700_bib36","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ceb.2007.10.006","article-title":"Life and death decisions by the E2F transcription factors","volume":"19","author":"Iaquinta","year":"2007","journal-title":"Curr Opin Cell Biol."},{"key":"2026060910070936700_bib37","doi-asserted-by":"publisher","first-page":"4176","DOI":"10.1016\/j.molcel.2022.09.009","article-title":"Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming","volume":"82","author":"Jacobs","year":"2022","journal-title":"Mol. Cell"},{"key":"2026060910070936700_bib38","doi-asserted-by":"publisher","first-page":"eaan4673","DOI":"10.1126\/science.aan4673","article-title":"Clonal hematopoiesis in human aging and disease","volume":"366","author":"Jaiswal","year":"2019","journal-title":"Science"},{"key":"2026060910070936700_bib39","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.stem.2024.05.010","article-title":"Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging","volume":"31","author":"Jakobsen","year":"2024","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib40","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.14844","article-title":"Immune reconstitution and survival of patients after allogeneic hematopoietic stem cell transplantation from older donors","volume":"37","author":"Jiang","year":"2023","journal-title":"Clin. Transpl."},{"key":"2026060910070936700_bib41","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1182\/blood.2023021426","article-title":"Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle","volume":"144","author":"Johnson","year":"2024","journal-title":"Cell"},{"key":"2026060910070936700_bib42","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.cell.2017.12.031","article-title":"BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis","volume":"172","author":"Kaufmann","year":"2018","journal-title":"Cell"},{"key":"2026060910070936700_bib43","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41590-021-00925-1","article-title":"A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness","volume":"22","author":"Kaufmann","year":"2021","journal-title":"Nat. Immunol."},{"key":"2026060910070936700_bib44","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/j.celrep.2017.04.074","article-title":"Proliferation drives aging-related functional decline in a subpopulation of the hematopoietic stem cell compartment","volume":"19","author":"Kirschner","year":"2017","journal-title":"Cell Rep."},{"key":"2026060910070936700_bib45","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1182\/blood.V98.7.2043","article-title":"Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: The effect of donor age","volume":"98","author":"Kollman","year":"2001","journal-title":"Blood"},{"key":"2026060910070936700_bib46","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1038\/s41467-025-57096-y","article-title":"Continuous map of early hematopoietic stem cell differentiation across human lifetime","volume":"16","author":"Komic","year":"2025","journal-title":"Nat. Commun."},{"key":"2026060910070936700_bib47","doi-asserted-by":"publisher","first-page":"13814","DOI":"10.1073\/pnas.0906556106","article-title":"Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage","volume":"106","author":"Kruse","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib48","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/j.1474-9726.2011.00675.x","article-title":"Age-related changes in human hematopoietic stem\/progenitor cells","volume":"10","author":"Kuranda","year":"2011","journal-title":"Aging Cell"},{"key":"2026060910070936700_bib49","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1097\/01.TP.0000173649.99261.DF","article-title":"Nonmyeloablative conditioning does not prevent telomere shortening after allogeneic stem cell transplantation","volume":"80","author":"Lahav","year":"2005","journal-title":"Transplantation"},{"key":"2026060910070936700_bib50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw227","article-title":"VarDict: A novel and versatile variant caller for next-generation sequencing in cancer research","volume":"44","author":"Lai","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2026060910070936700_bib51","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.stem.2015.01.017","article-title":"CDK6 levels regulate quiescence exit in human hematopoietic stem cells","volume":"16","author":"Laurenti","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib52","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nature25022","article-title":"From haematopoietic stem cells to complex differentiation landscapes","volume":"553","author":"Laurenti","year":"2018","journal-title":"Nature"},{"key":"2026060910070936700_bib53","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41592-024-02495-0","article-title":"The dynamics of hematopoiesis over the human lifespan","volume":"22","author":"Li","year":"2025","journal-title":"Nat. Methods"},{"key":"2026060910070936700_bib54","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2026060910070936700_bib55","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1182\/blood-2004-11-4282","article-title":"Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells","volume":"106","author":"Liang","year":"2005","journal-title":"Blood"},{"key":"2026060910070936700_bib56","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1016\/j.celrep.2016.08.064","article-title":"Bcl11a deficiency leads to hematopoietic stem cell defects with an aging-like phenotype","volume":"16","author":"Luc","year":"2016","journal-title":"Cell Rep."},{"key":"2026060910070936700_bib57","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nature16500","article-title":"Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential","volume":"529","author":"Luchsinger","year":"2016","journal-title":"Nature"},{"key":"2026060910070936700_bib58","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/S0026-0495(03)00295-6","article-title":"Interacting mediators of allostasis and allostatic load: Towards an understanding of resilience in aging","volume":"52","author":"McEwen","year":"2003","journal-title":"Metabolism"},{"key":"2026060910070936700_bib59","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1182\/bloodadvances.2022009240","article-title":"Haploidentical vs matched unrelated donors for patients with ALL: Donor age matters more than donor type","volume":"7","author":"Mehta","year":"2023","journal-title":"Blood Adv."},{"key":"2026060910070936700_bib60","doi-asserted-by":"publisher","first-page":"3387","DOI":"10.1182\/blood.2021013450","article-title":"Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans","volume":"139","author":"Mende","year":"2022","journal-title":"Blood"},{"key":"2026060910070936700_bib61","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.stem.2010.05.016","article-title":"A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal","volume":"7","author":"Milyavsky","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib62","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1084\/jem.20091318","article-title":"Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment","volume":"207","author":"Morita","year":"2010","journal-title":"J. Exp. Med."},{"key":"2026060910070936700_bib63","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/nm0996-1011","article-title":"The aging of hematopoietic stem cells","volume":"2","author":"Morrison","year":"1996","journal-title":"Nat. Med."},{"key":"2026060910070936700_bib64","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41586-022-04919-3","article-title":"Inflammatory memory and tissue adaptation in sickness and in health","volume":"607","author":"Naik","year":"2022","journal-title":"Nature"},{"key":"2026060910070936700_bib65","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nature24271","article-title":"Inflammatory memory sensitizes skin epithelial stem cells to tissue damage","volume":"550","author":"Naik","year":"2017","journal-title":"Nature"},{"key":"2026060910070936700_bib66","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1126\/science.1201219","article-title":"Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment","volume":"333","author":"Notta","year":"2011","journal-title":"Science"},{"key":"2026060910070936700_bib67","doi-asserted-by":"publisher","first-page":"aab2116","DOI":"10.1126\/science.aab2116","article-title":"Distinct routes of lineage development reshape the human blood hierarchy across ontogeny","volume":"351","author":"Notta","year":"2016","journal-title":"Science"},{"key":"2026060910070936700_bib68","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/nm.3651","article-title":"Stem cell aging: Mechanisms, regulators and therapeutic opportunities","volume":"20","author":"Oh","year":"2014","journal-title":"Nat. Med."},{"key":"2026060910070936700_bib70","doi-asserted-by":"publisher","first-page":"20012","DOI":"10.1073\/pnas.1116110108","article-title":"Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age","volume":"108","author":"Pang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib71","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1053\/j.seminhematol.2016.10.004","article-title":"Age-associated changes in human hematopoietic stem cells","volume":"54","author":"Pang","year":"2017","journal-title":"Semin. Hematol."},{"key":"2026060910070936700_bib72","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12877-016-0382-3","article-title":"Performance of Edmonton frail Scale on frailty assessment: Its association with multi-dimensional geriatric conditions assessed with specific screening tools","volume":"17","author":"Perna","year":"2017","journal-title":"BMC Geriatr."},{"key":"2026060910070936700_bib73","doi-asserted-by":"publisher","first-page":"17692","DOI":"10.1073\/pnas.0707045104","article-title":"Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development","volume":"104","author":"Pimanda","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib74","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1182\/blood.2023022666","article-title":"Circulating hematopoietic stem\/progenitor cell subsets contribute to human hematopoietic homeostasis","volume":"143","author":"Quaranta","year":"2024","journal-title":"Blood"},{"key":"2026060910070936700_bib75","doi-asserted-by":"publisher","first-page":"9194","DOI":"10.1073\/pnas.0503280102","article-title":"Cell intrinsic alterations underlie hematopoietic stem cell aging","volume":"102","author":"Rossi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib76","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1101\/gad.9.14.1753","article-title":"Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo","volume":"9","author":"Sauvageau","year":"1995","journal-title":"Genes Dev."},{"key":"2026060910070936700_bib77","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1038\/s41467-023-38448-y","article-title":"Hematopoietic reconstitution dynamics of mobilized- and bonemarrow-derived human hematopoietic stem cells after gene therapy","volume":"14","author":"Scala","year":"2023","journal-title":"Nat. Commun."},{"key":"2026060910070936700_bib78","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.stem.2021.10.002","article-title":"Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity","volume":"29","author":"Sch\u00f6nberger","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib79","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/s41587-019-0282-0","article-title":"Author Correction: Characterization of cell fate probabilities in single-cell data with Palantir","volume":"37","author":"Setty","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2026060910070936700_bib80","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1182\/blood-2017-07-746453","article-title":"Age-related clonal hematopoiesis","volume":"131","author":"Shlush","year":"2018","journal-title":"Blood"},{"key":"2026060910070936700_bib81","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1182\/blood-2007-01-069401","article-title":"Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia","volume":"110","author":"Signer","year":"2007","journal-title":"Blood"},{"key":"2026060910070936700_bib82","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.stem.2010.07.011","article-title":"The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche","volume":"7","author":"Simsek","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib83","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1093\/nar\/28.1.352","article-title":"dbSNP: a database of single nucleotide polymorphisms","volume":"28","author":"Smigielski","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2026060910070936700_bib84","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s41586-024-08128-y","article-title":"Clonal dynamics after allogeneic haematopoietic cell transplantation","volume":"635","author":"Spencer Chapman","year":"2024","journal-title":"Nature"},{"key":"2026060910070936700_bib85","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1182\/blood-2017-07-746446","article-title":"Anemia at older age: Etiologies, clinical implications, and management","volume":"131","author":"Stauder","year":"2018","journal-title":"Blood"},{"key":"2026060910070936700_bib86","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2026060910070936700_bib87","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026060910070936700_bib88","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1084\/jem.192.9.1273","article-title":"Age-associated characteristics of murine hematopoietic stem cells","volume":"192","author":"Sudo","year":"2000","journal-title":"J. Exp. Med."},{"key":"2026060910070936700_bib89","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.stem.2014.03.002","article-title":"Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal","volume":"14","author":"Sun","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib90","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.stem.2020.11.001","article-title":"The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization","volume":"28","author":"Takayama","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib91","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.stem.2013.11.021","article-title":"Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion","volume":"14","author":"van Galen","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib92","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031523","article-title":"Contribution of an aged microenvironment to aging-associated myeloproliferative disease","volume":"7","author":"Vas","year":"2012","journal-title":"PLoS One"},{"key":"2026060910070936700_bib93","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1038\/s41375-021-01337-8","article-title":"Clonal hematopoiesis and its emerging effects on cellular therapies","volume":"35","author":"von Bonin","year":"2021","journal-title":"Leukemia"},{"key":"2026060910070936700_bib94","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nature14131","article-title":"Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells","volume":"520","author":"Walter","year":"2015","journal-title":"Nature"},{"key":"2026060910070936700_bib95","doi-asserted-by":"publisher","first-page":"60764","DOI":"10.18632\/oncotarget.18485","article-title":"Changes of peripheral lymphocyte subsets and cytokine environment during aging and deteriorating gastrointestinal tract health status","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"2026060910070936700_bib96","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1182\/blood.V89.11.3919","article-title":"Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay","volume":"89","author":"Wang","year":"1997","journal-title":"Blood"},{"key":"2026060910070936700_bib97","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.molcel.2023.05.035","article-title":"Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner","volume":"83","author":"Wang","year":"2023","journal-title":"Mol. Cell"},{"key":"2026060910070936700_bib98","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.stem.2019.09.008","article-title":"Sphingolipid modulation activates proteostasis programs to govern human hematopoietic stem cell self-renewal","volume":"25","author":"Xie","year":"2019","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib99","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1158\/2643-3230.BCD-20-0155","article-title":"Sphingosine-1-phosphate receptor 3 potentiates inflammatory programs in normal and leukemia stem cells to promote differentiation","volume":"2","author":"Xie","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"2026060910070936700_bib100","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1084\/jem.20160923","article-title":"ETV2\/ER71 regulates hematopoietic regeneration by promoting hematopoietic stem cell proliferation","volume":"214","author":"Xu","year":"2017","journal-title":"J. Exp. Med."},{"key":"2026060910070936700_bib101","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1016\/j.stem.2021.03.017","article-title":"Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging","volume":"28","author":"Young","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026060910070936700_bib102","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.11.557271","article-title":"A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis","author":"Zeng","year":"2023","journal-title":"bioRxiv"},{"key":"2026060910070936700_bib103","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.11.557271","article-title":"Identification of a human hematopoietic stem cell subset that retains memory of inflammatory stress","author":"Zeng","year":"2023","journal-title":"bioRxiv"},{"key":"2026060910070936700_bib104","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol."},{"key":"2026060910070936700_bib105","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/s41556-022-00931-x","article-title":"Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells","volume":"24","author":"Zhang","year":"2022","journal-title":"Nat. Cell Biol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20251805\/1957122\/jem_20251805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20251805\/1957122\/jem_20251805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:07:23Z","timestamp":1781014043000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/223\/2\/e20251805\/278770\/Molecular-and-phenotypic-blueprint-of-human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":106,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,2]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20251805","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,30]]},"article-number":"e20251805"}}