TY - JOUR
T1 - Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
AU - Bedard, Mary C.
AU - Chihanga, Tafadzwa
AU - Carlile, Adrean
AU - Jackson, Robert
AU - Brusadelli, Marion G.
AU - Lee, Denis
AU - VonHandorf, Andrew
AU - Rochman, Mark
AU - Dexheimer, Phillip J.
AU - Chalmers, Jeffrey
AU - Nuovo, Gerard
AU - Lehn, Maria
AU - Williams, David E.J.
AU - Kulkarni, Aditi
AU - Carey, Molly
AU - Jackson, Amanda
AU - Billingsley, Caroline
AU - Tang, Alice
AU - Zender, Chad
AU - Patil, Yash
AU - Wise-Draper, Trisha M.
AU - Herzog, Thomas J.
AU - Ferris, Robert L.
AU - Kendler, Ady
AU - Aronow, Bruce J.
AU - Kofron, Matthew
AU - Rothenberg, Marc E.
AU - Weirauch, Matthew T.
AU - Van Doorslaer, Koenraad
AU - Wikenheiser-Brokamp, Kathryn A.
AU - Lambert, Paul F.
AU - Adam, Mike
AU - Steven Potter, S.
AU - Wells, Susanne I.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-37377-0
DO - 10.1038/s41467-023-37377-0
M3 - Article
C2 - 37031202
AN - SCOPUS:85151963373
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1975
ER -