{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:33:45Z","timestamp":1791516825163,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30AG086001"],"award-info":[{"award-number":["F30AG086001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32CA009056"],"award-info":[{"award-number":["T32CA009056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM008042"],"award-info":[{"award-number":["T32GM008042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM152342"],"award-info":[{"award-number":["T32GM152342"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi\u2010stage process of HSPC migration, and the cross\u2010talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T cell differentiation of phenotypically defined HSPCs from young and aged bone marrow using the Artificial Thymic Organoid (ATO) system, an in\u00a0vitro model which allows quantification of T cell differentiation from single HSPCs within a controlled microenvironment. Phenotypically, most HSCs from young bone marrow were CD150\n                    <jats:sup>lo<\/jats:sup>\n                    lymphoid\u2010biased (Ly\u2010HSC), whereas aged HSCs were predominantly CD150\n                    <jats:sup>hi<\/jats:sup>\n                    myeloid\u2010biased (My\u2010HSC). Clonal analysis showed Ly\u2010HSCs had greater T cell potential than My\u2010HSCs, but aging had little if any impact on T cell output from the same immunophenotypic HSC. Further, clonal studies of early thymic progenitors (ETPs) demonstrated comparable T cell potential in young and aged cells. We conclude that the hematopoietic contribution to thymic insufficiency during aging is likely due to a relative shift in the aged bone marrow to myeloid\u2010biased HSCs, rather than a per cell loss of T cell potential across HSPC in general. The profound changes that occur in the thymic microenvironment during aging likely also provide a major contribution to defects in thymopoiesis.\n                  <\/jats:p>","DOI":"10.1111\/acel.70615","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:12:04Z","timestamp":1782792724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clonal Analyses Reveal the Impact of Hematopoietic Stem and Progenitor Cell Aging on T Cell Development"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6579-9579","authenticated-orcid":false,"given":"Julia","family":"Gensheimer","sequence":"first","affiliation":[{"name":"Molecular Biology Interdepartmental Program University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"LaGosh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma R.","family":"Moulton","sequence":"additional","affiliation":[{"name":"Molecular Biology Interdepartmental Program University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"de Barros","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarnacion","family":"Montecino\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Yiu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-631X","authenticated-orcid":false,"given":"Kenneth","family":"Dorshkind","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gay M.","family":"Crooks","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"},{"name":"Molecular Biology Institute University of California, Los Angeles  Los Angeles California USA"},{"name":"Broad Stem Cell Research Center, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"},{"name":"Jonsson Comprehensive Cancer Center, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2020.06.011"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni878"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1524"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.2001.1848"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000834107"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.02.002"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201011\u2010123547"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100236\u20102"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111490"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008\u20108749(88)90315\u20102"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2024.104698"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12121314"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.026"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2003.tb03247.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201060464\u20103"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201001915\u20109"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201011\u20104282"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2326"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.1.245"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64096"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.01.016"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.12.011"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108320"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0996\u20101011"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102003\u201010\u20103448"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.4.1302.h81602001302_1302_1309"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201062703\u2010128\u20108_6"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890\u2010197609000\u201000010"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2016.12.008"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201006\u2010780882"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201001\u2010134858"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.155.2.432"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007238\u2010x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503280102"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2232"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20107613(02)00474\u20100"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4237"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2898810"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13870"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979\u2010020\u20100173\u20108"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.118.3.846"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600934"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201001\u2010071605"}],"container-title":["Aging 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