Data availability
The scRNA-sequencing data generated in this study have been deposited in the Gene Expression Omnibus (GEO) repository under accession number GSE237016, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237016]. Raw sequencing data and spatial transcriptomic data have been deposited in the dbGaP under accession number phs003405.v1.p1, [https://dbgap.ncbi.nlm.nih.gov/study/phs003405.v1.p1]. Xenium Ranger output files have been depostited in Zenodo under the accession number 17644360, [https://zenodo.org/records/17644360]. [Source data](https://www.nature.com/articles/s41467-025-67033-…
Data availability
The scRNA-sequencing data generated in this study have been deposited in the Gene Expression Omnibus (GEO) repository under accession number GSE237016, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237016]. Raw sequencing data and spatial transcriptomic data have been deposited in the dbGaP under accession number phs003405.v1.p1, [https://dbgap.ncbi.nlm.nih.gov/study/phs003405.v1.p1]. Xenium Ranger output files have been depostited in Zenodo under the accession number 17644360, [https://zenodo.org/records/17644360]. Source data are provided with this paper.
Code availability
No previously unreported or otherwise custom computer code was generated during this study.
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Acknowledgements
We thank Dale Cowley and the UNC Animal Models Core facility for the design and generation of the inducible Apobec3 mouse model. We thank the Pathology Services Core (PSC) for expert technical assistance. Both the PSC and the UNC Animal Models Core Facility are supported in part by an NCI Center Core Support Grant (P30CA016086). This work was supported by NIH F31CA247250 (A.S.T.), F31CA281339 (M.S.S.), NIH R01CA241810 and R01CA292625 (W.Y.K.), UNC Integrated Translational Oncology Program (iTOP), T32CA244125 (K.H.G. and W.B.), the University Cancer Research Fund (W.Y.K. and J.S.D.), and the Thomas M. Mohr Fund for Bladder Cancer Research.
Author information
Author notes
These authors contributed equally: Michael S. Sturdivant, Andrew S. Truong. 1.
These authors jointly supervised this work: Jeffrey S. Damrauer, and William Y. Kim.
Authors and Affiliations
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Michael S. Sturdivant, Andrew S. Truong, Mi Zhou, Elliott D. Toomer, Wolfgang Beckabir, John Raupp, Ujjawal Manocha, Tracy L. Rose, Matthew I. Milowsky, Sara E. Wobker, Kathryn H. Gessner, Jeffrey S. Damrauer & William Y. Kim 1.
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Michael S. Sturdivant, Andrew S. Truong, Elliott D. Toomer & William Y. Kim 1.
Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Ibardo A. Zambrano, Hung-Jui Tan, Marc A. Bjurlin, Angela B. Smith & Kathryn H. Gessner 1.
Department of Medicine, Division of Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Tracy L. Rose, Matthew I. Milowsky, Jeffrey S. Damrauer & William Y. Kim 1.
Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Sara E. Wobker 1.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kathryn H. Gessner & William Y. Kim
Authors
- Michael S. Sturdivant
- Andrew S. Truong
- Mi Zhou
- Elliott D. Toomer
- Wolfgang Beckabir
- John Raupp
- Ujjawal Manocha
- Ibardo A. Zambrano
- Hung-Jui Tan
- Marc A. Bjurlin
- Angela B. Smith
- Tracy L. Rose
- Matthew I. Milowsky
- Sara E. Wobker
- Kathryn H. Gessner
- Jeffrey S. Damrauer
- William Y. Kim
Contributions
Study conception: A.S.T., J.S.D., and W.Y.K. Experimental design: M.S.S., A.S.T., J.S.D, and W.Y.K. Sample acquisition and clinical annotation: H.J.T., M.A.B., A.B.S., T.L.R., M.I.M., S.E.W., and K.H.G. Data generation: M.S.S., A.S.T., M.Z., E.D.T., W.B., J.R., U.M., I.A.Z., S.E.W., and J.S.D. Data analysis and interpretation: M.S.S., A.S.T., M.Z., E.D.T., J.S.D., and W.Y.K. Manuscript writing: M.S.S., A.S.T., J.S.D, and W.Y.K. Manuscript editing and review: M.S.S., A.S.T., M.Z., E.D.T., W.B., J.R., U.M., I.A.Z., H.J.T., M.A.B., A.B.S., T.L.R., M.I.M., S.E.W., K.H.G., J.S.D., and W.Y.K.
Corresponding authors
Correspondence to Jeffrey S. Damrauer or William Y. Kim.
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Sturdivant, M.S., Truong, A.S., Zhou, M. et al. APOBEC3 promotes squamous differentiation via IL-1A/AP-1 signaling. Nat Commun (2025). https://doi.org/10.1038/s41467-025-67033-8
Received: 20 August 2023
Accepted: 20 November 2025
Published: 14 December 2025
DOI: https://doi.org/10.1038/s41467-025-67033-8