Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Nathan S. Gasek; Pengyi Yan; Junyu Zhu; K. Raman Purushothaman; Taewan Kim; Lichao Wang; Binsheng Wang; William F. Flynn; Mingda Sun; Chun Guo; Billy Huggins; Roshanak Sharafieh; Yueying Zhou; Vojtech Parizek; Tamar Tchkonia; James L. Kirkland; Saranya P. Wyles; Ming Xu

doi:10.1038/s43587-024-00755-4

Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Nathan S. Gasek
, Pengyi Yan
, Junyu Zhu
, K. Raman Purushothaman
, Taewan Kim
, Lichao Wang
, Binsheng Wang
, William F. Flynn
, Mingda Sun
, Chun Guo
, Billy Huggins
, Roshanak Sharafieh
, Yueying Zhou
, Vojtech Parizek
, Tamar Tchkonia
, James L. Kirkland
, Saranya P. Wyles
, Ming Xu

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.

Original language	English (US)
Article number	39553
Pages (from-to)	21-27
Number of pages	7
Journal	Nature Aging
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s43587-024-00755-4
State	Published - Jan 2025
Externally published	Yes

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Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

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10.1038/s43587-024-00755-4

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Gasek, N. S., Yan, P., Zhu, J., Purushothaman, K. R., Kim, T., Wang, L., Wang, B., Flynn, W. F., Sun, M., Guo, C., Huggins, B., Sharafieh, R., Zhou, Y., Parizek, V., Tchkonia, T., Kirkland, J. L., Wyles, S. P., & Xu, M. (2025). Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing. Nature Aging, 5(1), 21-27. Article 39553. https://doi.org/10.1038/s43587-024-00755-4

Gasek, NS, Yan, P, Zhu, J, Purushothaman, KR, Kim, T, Wang, L, Wang, B, Flynn, WF, Sun, M, Guo, C, Huggins, B, Sharafieh, R, Zhou, Y, Parizek, V, Tchkonia, T, Kirkland, JL, Wyles, SP & Xu, M 2025, 'Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing', Nature Aging, vol. 5, no. 1, 39553, pp. 21-27. https://doi.org/10.1038/s43587-024-00755-4

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title = "Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing",

abstract = "While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.",

author = "Gasek, \{Nathan S.\} and Pengyi Yan and Junyu Zhu and Purushothaman, \{K. Raman\} and Taewan Kim and Lichao Wang and Binsheng Wang and Flynn, \{William F.\} and Mingda Sun and Chun Guo and Billy Huggins and Roshanak Sharafieh and Yueying Zhou and Vojtech Parizek and Tamar Tchkonia and Kirkland, \{James L.\} and Wyles, \{Saranya P.\} and Ming Xu",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

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month = jan,

doi = "10.1038/s43587-024-00755-4",

language = "English (US)",

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AU - Gasek, Nathan S.

AU - Yan, Pengyi

AU - Zhu, Junyu

AU - Purushothaman, K. Raman

AU - Kim, Taewan

AU - Wang, Lichao

AU - Wang, Binsheng

AU - Flynn, William F.

AU - Sun, Mingda

AU - Guo, Chun

AU - Huggins, Billy

AU - Sharafieh, Roshanak

AU - Zhou, Yueying

AU - Parizek, Vojtech

AU - Tchkonia, Tamar

AU - Kirkland, James L.

AU - Wyles, Saranya P.

AU - Xu, Ming

PY - 2025/1

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N2 - While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.

AB - While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.

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Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Abstract

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