Academic Journal
A cross-talk between p16High senescence and cellular reprogramming.
| Title: | A cross-talk between p16High senescence and cellular reprogramming. |
|---|---|
| Authors: | Emelyanov A; Institute for Research on Cancer and Aging of Nice (IRCAN), Université Côte d'Azur, INSERM, CNRS, Nice, France., Bulavin DV; Institute for Research on Cancer and Aging of Nice (IRCAN), Université Côte d'Azur, INSERM, CNRS, Nice, France. |
| Source: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2026 Jun 10; Vol. 140 (6), pp. 1137-1147. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society Original Publication: London, Medical Research Society. |
| MeSH Terms: | Cellular Senescence*/genetics , Cellular Senescence*/physiology , Cyclin-Dependent Kinase Inhibitor p16*/metabolism , Cyclin-Dependent Kinase Inhibitor p16*/genetics , Cellular Reprogramming*, Fibroblasts/metabolism ; Humans ; Kruppel-Like Factor 4 ; Animals ; Epigenesis, Genetic ; Signal Transduction |
| Abstract: | Cellular senescence and OSKM (Oct4, Sox2, Klf4, and Myc)-mediated reprogramming represent interconnected biological programs that both play important roles in regulating cellular plasticity. Recent studies have highlighted the role of p16-driven senescence in establishing a stable barrier to reprogramming by limiting epigenetic flexibility. Mechanistically, p16High senescent fibroblasts enforce this barrier through stress-induced and AP-1-driven epigenetic remodeling and NNMT-mediated metabolic SAM depletion, which restricts methylation-dependent chromatin remodeling in both p16High and neighboring p16Low cells via a paracrine mechanism. Conversely, clearance of p16High cells restores SAM levels and enhances cellular plasticity in neighboring cells, enabling the acquisition of totipotent-like states during reprogramming. Within p16High cells themselves, reprogramming can reverse some features of senescence, restoring more youthful cellular states under controlled conditions. Importantly, p16High cells remain highly resistant to full reprogramming, minimizing the risk of teratoma and tumor formation in vivo and making them promising target for rejuvenation strategies based on partial reprogramming. In this review, we examine the molecular interplay between p16High senescence and reprogramming, highlighting their dual roles as both barriers to and facilitators of cell fate transitions. (© 2026 The Author(s).) |
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| Grant Information: | N/A Agence Nationale de la Recherche (ANR) |
| Contributed Indexing: | Keywords: induced pluripotent stem cells; p16; partial reprogramming; reprogramming; senescence |
| Substance Nomenclature: | 0 (Kruppel-Like Factor 4) 0 (Cyclin-Dependent Kinase Inhibitor p16) 0 (KLF4 protein, human) |
| Entry Date(s): | Date Created: 20260529 Date Completed: 20260717 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13229649 |
| DOI: | 10.1042/CS20260240 |
| PMID: | 42212384 |
| Database: | MEDLINE |
| ISSN: | 1470-8736 |
|---|---|
| DOI: | 10.1042/CS20260240 |