{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:30Z","timestamp":1790574930695,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471050"],"award-info":[{"award-number":["82471050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070936"],"award-info":[{"award-number":["82070936"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018806","name":"Department of Science and Technology of Hubei Province","doi-asserted-by":"publisher","award":["2024DJC066"],"award-info":[{"award-number":["2024DJC066"]}],"id":[{"id":"10.13039\/501100018806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017958","name":"Health Commission of Hubei Province","doi-asserted-by":"publisher","award":["WJ2021ZH0005"],"award-info":[{"award-number":["WJ2021ZH0005"]}],"id":[{"id":"10.13039\/100017958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD). However, their clinical application is constrained by replicative aging during in\u00a0vitro expansion. In this study, we investigated whether a three\u2010dimensional (3D) Matrigel\u2010based culture system could modulate replicative aging in LNCs. Compared with conventional two\u2010dimensional (2D) culture, 3D\u2010cultured LNCs restored stemness marker expression and enhanced proliferative capacity. Concurrently, these cells displayed reduced senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal) activity and decreased expression of senescence\u2010associated proteins, including p16, p21, p53, and \u03b3\u2010H2AX. Single\u2010cell RNA sequencing (scRNA\u2010seq) analysis revealed prominent upregulation of FOS\u2010like antigen 1 (FOSL1). FOSL1 is a component of the AP\u20101 transcription factor family and participates in cell proliferation and stress adaptation. Functional assays using an in\u00a0vitro replicative aging model showed that FOSL1 knockdown in early\u2010passage (P4) LNCs accelerated senescence, whereas FOSL1 overexpression in late\u2010passage (P11) LNCs attenuated senescence. Mechanistically, FOSL1 knockdown induced mitochondrial dysfunction characterized by elevated levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), as well as a decrease in mitochondrial membrane potential, while FOSL1 overexpression preserved mitochondrial integrity and function. Collectively, our findings demonstrate that 3D culture reverses LNC replicative aging through FOSL1\u2010mediated enhancement of mitochondrial function, providing a microenvironment\u2010based strategy to counteract replicative aging in adult stem cells for corneal regenerative therapy.<\/jats:p>","DOI":"10.1111\/acel.70705","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:10:18Z","timestamp":1788934218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>3D<\/scp>\n                    Culture Reverses Limbal Niche Cell Replicative Aging via\n                    <scp>FOSL1<\/scp>\n                    Upregulation"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5162-4460","authenticated-orcid":false,"given":"Xuying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Tongji Hospital, Tongji Medical 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