{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kousa AI"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","Cancer Council Victoria","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","NIA NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","U.S. Department of Health & Human Services | NIH | National Institute on Aging","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","NHLBI NIH HHS","European Molecular Biology Organization (EMBO)","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)","Department of Health | National Health and Medical Research Council","European Molecular Biology Organization","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)","Department of Health | National Health and Medical Research Council (NHMRC)","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)","NIGMS NIH HHS"],"pagination":["1593-1606"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11362016"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(9)"],"pubmed_abstract":["The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals."],"journal":["Nature immunology"],"pubmed_title":["Age-related epithelial defects limit thymic function and regeneration."],"pmcid":["PMC11362016"],"funding_grant_id":["R01-HL145276","P30 CA008748","T32 GM007103","R01 HL147584","P01 AG052359","R35-HL-171556","R01 HL165673","P30-CA015704","P01 CA023766","R01-HL147584","R01-HL165673","R01 CA228358","ALTF-431-2017","1146518","P01-AG052359","P30 CA015704","R01 HL123340","T32-GM007270","1187367","1090236","1078763","F30 HL165761","1121325","U01 AI170035","R01-CA228308","R01 HL145276","K08 CA293271","R35 HL171556","1102104","R01-HL123340","R01 CA228308","1158024","F30-HL165761","U01-AI70035","T32 GM007270"],"pubmed_authors":["Rogers KL","Cooper K","Lee N","van den Brink MRM","Wimmer VC","Jahn L","Gomes ALC","Acenas D","Lederer E","Lemarquis AL","Malard F","Gipson B","Dudakov JA","Argyropoulos KV","Sikkema L","Youssef S","Granadier D","Andrlova H","Hale L","Manley NR","Kousa AI","Gray DHD","Zhao K","Lazrak A","Mazutis L","Pe'er D","Docampo M","Setty M","D'Andrea M","Nichols K","Sharma R","Burgos da Silva M","Sheridan JM","Tsai J","Velardi E","DeWolf S","Ghale R","Flores AE"],"additional_accession":[]},"is_claimable":false,"name":"Age-related epithelial defects limit thymic function and regeneration.","description":"The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-01T20:33:57.891Z","creation":"2025-02-19T02:34:24.083Z"},"accession":"S-EPMC11362016","cross_references":{"pubmed":["39112630"],"doi":["10.1038/s41590-024-01915-9"]}}