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T cells experience the TCR recombination to generate diversity, self\u2010antigen tolerance, and immune response. However, the spatial heterogeneity of transcriptomics and immune repertoire of the thymus during aging haven't been studied. We constructed the thymus's spatial transcriptomics and spatial immune repertoire atlas by TCR\u2010specific amplification. The integrated multi\u2010omics analysis of the scRNA\u2010seq, ST\u2010seq, spatial\u2010TCR\u2010seq, scTCR\u2010seq, and TCR\u2010seq was developed to investigate the thymus during aging. ST\u2010seq demonstrated that the heterogeneity of the cortex and a novel cortex subset associated with progenitor cell differentiation was identified. Proliferating CD69negDN T cells decreased and regulatory CD4SP T cells increased during aging. Using deconvolution analyses, the spatial distribution of T cell subsets was revealed. The spatial distribution of TCR recombination and distinct thymic selection processes were illustrated. Pseudo\u2010time analyses demonstrated differentiation order and spatial migration route of T cells. The novel spatial\u2010TCR\u2010seq demonstrated the overall spatial distribution of TCR, the TCR pairing process, and their dynamic features under thymic selection pressure which revealed that TRB clonotypes with hydrophilic and low\u2010pI CDR3s tended to pass the negative selection opposite to the positive selection. The positive selection pressure of the thymus diminishes during the aging process. A TCR maturation scoring system using TCR\u2010seq was developed to identify TCR clonotypes that tended to mature. All boost the thymus study into the era of spatial immune repertoire and transcriptome and widen our knowledge about T cell development.<\/jats:p>","DOI":"10.1111\/acel.70631","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:01:30Z","timestamp":1785038490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single Cell and Spatially Resolved Transcriptome and Immune Repertoire of Mouse Thymus During Aging Reveal Immunological Heterogeneity and Direction of Thymic Selection Pressure"],"prefix":"10.1111","volume":"25","author":[{"given":"Jialing","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Pediatric Research Institute Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory 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Hubei University of Science and Technology  Xianning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kindstar Global Precision Medicine Institute  Wuhan China"},{"name":"Wuhan Kindstar Biotech Technology Co., Ltd  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Xu","sequence":"additional","affiliation":[{"name":"Kindstar Global Precision Medicine Institute  Wuhan China"},{"name":"Wuhan Kindstar Biotech Technology Co., Ltd  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Special Biomedicine, School of Medicine Guangxi University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongshun","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Center, the Eighth Affiliated 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