Abstract
Adult stem cells and their niches communicate intricately for tissue maintenance and regeneration. However, effectively coordinating these complex interactions is challenging. Here, we demonstrate that transient dedifferentiation of a fraction of epithelial stem cell progenies orchestrates beneficial changes within the entire skin’s cellular networks to favor repair. We achieved this by inducing a mosaic and reversible expression of reprogramming factors (Oct-4, Sox2, Klf4, and c-Myc) in the mouse epidermis. This in vivo partial epidermal reprogramming not only affected the partially reprogrammed cells, but also their microenvironment, including neighboring epithelial cells and T cells, conferring widespread healing characteristics even in the absence of injury. When a wound was introduced, these collective changes accelerated re-epithelialization in both wild-type and a hyperglycemic mouse disease model. Furthermore, the effects extended to dermal healing, leading to reduced scarring and altered angiogenesis. In conclusion, our work reveals that mosaic partial reprogramming of the epidermis influences various cell types within the skin during homeostasis and repair, leading to enhanced cutaneous wound healing.
Data availability
All scRNA-seq data are deposited in the SRA database and are publicly available under accession code PRJNA1139235. All other data supporting the findings of this study are provided in the Source data. Source data are provided with this paper.
Code availability
All original codes generated during scRNA-seq analysis are available at the following GitHub repository: https://github.com/CB-postech/scRNA-seq_mouse_Epi-iOSKM.
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Acknowledgements
We thank the members of Choi Laboratory for their helpful discussions and comments on this manuscript. This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (NRF-RS-2025-00560319, NRF-RS-2022-NR072134, NRF-RS-2022-NR067309, NRF-RS-2023-00223298, and NRF-RS-2024-00433755 to S.C.; NRF-RS-2024-00426031 to J.K.K.; NRF-RS-2023-00221112 to J.K.K. and S.C.). S.C. has been supported by a POSCO Science Fellowship from the POSCO TJ Park Foundation. M.K., E.C., Y.J., B.K., C.L., J.L., J.K.K. and S.C. were supported by a BK21 FOUR Research Fellowship funded by the Ministry of Education, Republic of Korea.
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S.C., M.K., and Y.J. conceived the project. M.K., Y.J., and B.K. performed most of the experiments and quantified and analyzed the data. E.C. and J.K.K. performed the bioinformatic analysis. Y.H.C. generated RNA-seq libraries. C.L. performed flow cytometry. J.L. performed splinted full-thickness cutaneous wounding. J.H.L, K.-P.K., and B.-K.K. provided intellectual input. J.K.K. and S.C. acquired funding. M.K., Y.J., J.K.K., and S.C. wrote the manuscript, with discussion and feedback from all co-authors.
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Kwak, M., Choi, E., Jo, Y. et al. Mosaic partial epidermal reprogramming remodels neighbors and niches to refine skin homeostasis and repair. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69047-2
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DOI: https://doi.org/10.1038/s41467-026-69047-2
