{"title":"On the mechanisms of epidermal stemness and differentiation.","authors":"Saumya Shukla, Raghvendra Singh","doi":"10.1038/s41540-025-00581-3","DOIUrl":null,"url":null,"abstract":"<p><p>High Wnt and low Notch activities characterize epidermal stem cells (SCs), while low Wnt and high Notch activities characterize the terminally differentiated epidermal cells (TDCs). However, the mechanism by which transit amplifying cells (TACs) are induced to become terminally differentiated remains unclear. Our analysis suggests that oscillations in Wnt, Notch, and YAP/TAZ activities lead to the production of TDCs from TACs. Furthermore, the role of stem cell markers in epidermal differentiation, regeneration, and the functional aspects of the epidermis remains unclear. Here, based on the ability of the epidermal SCs to induce the differentiation of TACs, we characterize the SCs as having the expression of Notch ligand, Delta, higher than a critical value. Further, we have functionally defined the critical value of the Delta expression by SCs. Our paper may have general implications for the stemness and differentiation of other tissues.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"106"},"PeriodicalIF":3.5000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485183/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Systems Biology and Applications","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41540-025-00581-3","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
High Wnt and low Notch activities characterize epidermal stem cells (SCs), while low Wnt and high Notch activities characterize the terminally differentiated epidermal cells (TDCs). However, the mechanism by which transit amplifying cells (TACs) are induced to become terminally differentiated remains unclear. Our analysis suggests that oscillations in Wnt, Notch, and YAP/TAZ activities lead to the production of TDCs from TACs. Furthermore, the role of stem cell markers in epidermal differentiation, regeneration, and the functional aspects of the epidermis remains unclear. Here, based on the ability of the epidermal SCs to induce the differentiation of TACs, we characterize the SCs as having the expression of Notch ligand, Delta, higher than a critical value. Further, we have functionally defined the critical value of the Delta expression by SCs. Our paper may have general implications for the stemness and differentiation of other tissues.
期刊介绍：
npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology.
We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.
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