Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer

Mary C. Bedard, Tafadzwa Chihanga, Adrean Carlile, Robert Jackson, Marion G. Brusadelli, Denis Lee, Andrew VonHandorf, Mark Rochman, Phillip J. Dexheimer, Jeffrey Chalmers, Gerard Nuovo, Maria Lehn, David E.J. Williams, Aditi Kulkarni, Molly Carey, Amanda Jackson, Caroline Billingsley, Alice Tang, Chad Zender, Yash PatilTrisha M. Wise-Draper, Thomas J. Herzog, Robert L. Ferris, Ady Kendler, Bruce J. Aronow, Matthew Kofron, Marc E. Rothenberg, Matthew T. Weirauch, Koenraad Van Doorslaer, Kathryn A. Wikenheiser-Brokamp, Paul F. Lambert, Mike Adam, S. Steven Potter, Susanne I. Wells

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle is dependent on the differentiation program of stratified squamous epithelium, but the landscape of keratinocyte subpopulations which support distinct phases of the viral life cycle has yet to be elucidated. Here, single cell RNA sequencing of HPV16 infected compared to uninfected organoids identifies twelve distinct keratinocyte populations, with a subset mapped to reconstruct their respective 3D geography in stratified squamous epithelium. Instead of conventional terminally differentiated cells, an HPV-reprogrammed keratinocyte subpopulation (HIDDEN cells) forms the surface compartment and requires overexpression of the ELF3/ESE-1 transcription factor. HIDDEN cells are detected throughout stages of human carcinogenesis including primary human cervical intraepithelial neoplasias and HPV positive head and neck cancers, and a possible role in promoting viral carcinogenesis is supported by TCGA analyses. Single cell transcriptome information on HPV-infected versus uninfected epithelium will enable broader studies of the role of individual keratinocyte subpopulations in tumor virus infection and cancer evolution.

Original languageEnglish (US)
Article number1975
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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