biostudies-literatureBedard MCNIDCR NIH HHSNIAID NIH HHSNIEHS NIH HHSCancerFreeKidsU.S. Department of Health & Human Services | NIH | National Cancer InstituteU.S. Department of Health & Human Services | NIH | National Institute of Environmental Health SciencesNHGRI NIH HHSNCI NIH HHSState of Arizona Improving Health TRIFThe BI05 Institute1975https://www.ebi.ac.uk/biostudies/studies/S-EPMC10082832biostudies-literatureUnknown14(1)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 stagesNature communicationsSingle cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer.PMC10082832R35 CA210807F30 AI157229T32ES007250R03 DE030211R01 CA228113R01 HG010730P01 CA022443P30 CA023074R01 AI165638U01 AI130830CA228113T32 ES007250Bedard MCAdam MTang AWeirauch MTBrusadelli MGKofron MCarlile ALee DChalmers JAronow BJKulkarni APatil YJackson ADexheimer PJVonHandorf AKendler AWells SIVan Doorslaer KWikenheiser-Brokamp KABillingsley CWise-Draper TMJackson RSteven Potter SNuovo GCarey MFerris RLLambert PFHerzog TJRothenberg MEChihanga TZender CRochman MWilliams DEJLehn MfalseSingle cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer.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 stages2023-01-01T00:00:00Z2023 Apr2026-07-15T01:33:07.362Z2024-11-08T21:08:45.695ZS-EPMC100828323703120210.1038/s41467-023-37377-0