{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:07:40Z","timestamp":1788883660087,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Epidermal keratinocytes (KCs) undergo a tightly orchestrated differentiation programme that culminates in the formation of a protective barrier between the body and the environment. Although this process has been studied extensively, several regulators that coordinate KC survival, stratification, and terminal differentiation remain incompletely defined. To identify mechanisms governing epidermal homeostasis, we compared transcriptomic profiles of undifferentiated KCs, KCs differentiated in monolayer culture, and fully stratified KCs in three-dimensional organotypic skin equivalents. Both differentiation models showed downregulation of cell-cycle-associated transcripts and induction of KC differentiation genes, whereas genes involved in extracellular-matrix organisation were preferentially induced in skin equivalents. Transcription-factor activity inference based on target gene expression identified the transcriptional repressor and ubiquitin\/SUMO E3 ligase TRIM28 as a candidate regulator of epidermal homeostasis. Single-cell RNA sequencing and immunostaining of human epidermis revealed strong TRIM28 expression throughout the living epidermal layers, with marked loss in the outermost terminally differentiated compartment. Functional depletion of TRIM28 in primary human KCs impaired epidermal development, increased apoptosis, and produced markedly thinner organotypic epidermis despite preserved stratification. TRIM28-deficient skin equivalents showed limited transcriptional reprogramming associated with reduced p53 ubiquitination, p53 accumulation, and apoptosis of basal KCs. Collectively, these findings identify TRIM28 as an important candidate regulator of epidermal homeostasis and suggest that TRIM28 supports epidermal expansion, at least in part, by contributing to p53 turnover.<\/jats:p>","DOI":"10.3389\/fcell.2026.1903169","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:23:49Z","timestamp":1788881029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TRIM28 contributes to epidermal homeostasis and is associated with altered p53 regulation"],"prefix":"10.3389","volume":"14","author":[{"given":"Lucian","family":"Beer","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"K\u00fchtreiber","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Aposcience AG","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Wagner","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology and Neuropharmacology, Centre of Physiology and Pharmacology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Golabi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie Alexandra","family":"R\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Salek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mildner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"vbac016","DOI":"10.1093\/bioadv\/vbac016","article-title":"decoupleR: ensemble of computational methods to infer biological activities from omics data","volume":"2","author":"Badia-I-Mompel","year":"2022","journal-title":"Bioinforma. 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