Author
Listed:
- Mary C. Bedard
(Cincinnati Children’s Hospital Medical Center)
- Tafadzwa Chihanga
(Cincinnati Children’s Hospital Medical Center)
- Adrean Carlile
(Cincinnati Children’s Hospital Medical Center)
- Robert Jackson
(University of Arizona)
- Marion G. Brusadelli
(Division of Clinical Operations, Medpace)
- Denis Lee
(University of Wisconsin)
- Andrew VonHandorf
(Cincinnati Children’s Hospital Medical Center)
- Mark Rochman
(Cincinnati Children’s Hospital Medical Center)
- Phillip J. Dexheimer
(Cincinnati Children’s Hospital Medical Center)
- Jeffrey Chalmers
(William G. Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University)
- Gerard Nuovo
(Ohio State University Medical Center)
- Maria Lehn
(University of Cincinnati College of Medicine)
- David E. J. Williams
(University of Arizona
University of Arizona)
- Aditi Kulkarni
(University of Pittsburgh
UPMC Hillman Cancer Center)
- Molly Carey
(University of Cincinnati Medical Center)
- Amanda Jackson
(University of Cincinnati Medical Center)
- Caroline Billingsley
(University of Cincinnati Medical Center)
- Alice Tang
(University of Cincinnati)
- Chad Zender
(University of Cincinnati)
- Yash Patil
(University of Cincinnati)
- Trisha M. Wise-Draper
(University of Cincinnati College of Medicine)
- Thomas J. Herzog
(University of Cincinnati Medical Center)
- Robert L. Ferris
(University of Pittsburgh
UPMC Hillman Cancer Center
University of Pittsburgh
University of Pittsburgh)
- Ady Kendler
(University of Cincinnati College of Medicine)
- Bruce J. Aronow
(Cincinnati Children’s Hospital Medical Center
Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine)
- Matthew Kofron
(Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine)
- Marc E. Rothenberg
(Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine)
- Matthew T. Weirauch
(Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine
Cincinnati Children’s Hospital Medical Center)
- Koenraad Doorslaer
(University of Arizona
University of Arizona
The BIO5 Institute, University of Arizona
University of Arizona)
- Kathryn A. Wikenheiser-Brokamp
(University of Cincinnati College of Medicine
Cincinnati Children’s Hospital Medical Center)
- Paul F. Lambert
(University of Wisconsin)
- Mike Adam
(Cincinnati Children’s Hospital Medical Center)
- S. Steven Potter
(Cincinnati Children’s Hospital Medical Center)
- Susanne I. Wells
(Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine)
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.
Suggested Citation
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 & Ma, 2023.
"Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer,"
Nature Communications, Nature, vol. 14(1), pages 1-20, December.
Handle:
RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37377-0
DOI: 10.1038/s41467-023-37377-0
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