학술논문
Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
Document Type
Original Paper
Author
Bedard, Mary C.; Chihanga, Tafadzwa; Carlile, Adrean; Jackson, Robert; Brusadelli, Marion G.; Lee, Denis; VonHandorf, Andrew; Rochman, Mark; Dexheimer, Phillip J.; Chalmers, Jeffrey; Nuovo, Gerard; Lehn, Maria; Williams, David E. J.; Kulkarni, Aditi; Carey, Molly; Jackson, Amanda; Billingsley, Caroline; Tang, Alice; Zender, Chad; Patil, Yash; Wise-Draper, Trisha M.; Herzog, Thomas J.; Ferris, Robert L.; Kendler, Ady; Aronow, Bruce J.; Kofron, Matthew; Rothenberg, Marc E.; Weirauch, Matthew T.; Van Doorslaer, Koenraad; Wikenheiser-Brokamp, Kathryn A.; Lambert, Paul F.; Adam, Mike; Steven Potter, S.; Wells, Susanne I.
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
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.
The role of keratinocyte subpopulations in the different phases of the viral cycle during HPV16 infection remains to be characterised. Here, single cell RNA sequencing of HPV16 infected and uninfected organoids identifies 12 distinct keratinocyte populations including an HPV-reprogrammed keratinocyte subpopulation that is linked to cancer.
The role of keratinocyte subpopulations in the different phases of the viral cycle during HPV16 infection remains to be characterised. Here, single cell RNA sequencing of HPV16 infected and uninfected organoids identifies 12 distinct keratinocyte populations including an HPV-reprogrammed keratinocyte subpopulation that is linked to cancer.