TY - JOUR
T1 - The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells
AU - Hu, Zhiyuan
AU - Artibani, Mara
AU - Alsaadi, Abdulkhaliq
AU - Wietek, Nina
AU - Morotti, Matteo
AU - Shi, Tingyan
AU - Zhong, Zhe
AU - Santana Gonzalez, Laura
AU - El-Sahhar, Salma
AU - KaramiNejadRanjbar, Mohammad
AU - Mallett, Garry
AU - Feng, Yun
AU - Masuda, Kenta
AU - Zheng, Yiyan
AU - Chong, Kay
AU - Damato, Stephen
AU - Dhar, Sunanda
AU - Campo, Leticia
AU - Garruto Campanile, Riccardo
AU - Soleymani majd, Hooman
AU - Rai, Vikram
AU - Maldonado-Perez, David
AU - Jones, Stephanie
AU - Cerundolo, Vincenzo
AU - Sauka-Spengler, Tatjana
AU - Yau, Christopher
AU - Ahmed, Ahmed Ashour
N1 - Funding Information:
We thank the WIMM Flow Cytometry Facility, Single Cell Facility, CBRG, and Wolfson Imaging Centre for their help in this study. We thank the Oxford Radcliffe Biobank and the Oxford Centre for Histopathology Research for their help with obtaining tissue samples. This work was supported by Ovarian Cancer Action and Oxford Biomedical Research Centre (BRC), National Institute for Health Research . C.Y. was supported by UK Medical Research Council Research Grants ( MR/L001411/1 and MR/P02646X/1 ), a Wellcome Trust Core Award grant number 090532/Z/09/Z , and by The Alan Turing Institute under EPSRC grant EP/N510129/1 . Z.H. was supported by the NIHR Oxford BRC. D.M.P. was funded by the NIHR Oxford BRC (Molecular Diagnostics Theme/Multimodal Pathology Subtheme). Y.F. was supported by the CRUK Oxford Centre.
Funding Information:
We thank the WIMM Flow Cytometry Facility, Single Cell Facility, CBRG, and Wolfson Imaging Centre for their help in this study. We thank the Oxford Radcliffe Biobank and the Oxford Centre for Histopathology Research for their help with obtaining tissue samples. This work was supported by Ovarian Cancer Action and Oxford Biomedical Research Centre (BRC), National Institute for Health Research. C.Y. was supported by UK Medical Research Council Research Grants (MR/L001411/1 and MR/P02646X/1), a Wellcome Trust Core Award grant number 090532/Z/09/Z, and by The Alan Turing Institute under EPSRC grant EP/N510129/1. Z.H. was supported by the NIHR Oxford BRC. D.M.P. was funded by the NIHR Oxford BRC (Molecular Diagnostics Theme/Multimodal Pathology Subtheme). Y.F. was supported by the CRUK Oxford Centre. Conceptualization, Project Administration, and Supervision, A.A.A. and C.Y.; Funding Acquisition, A.A.A. C.Y. and Y.F.; Investigation, A.A.A. C.Y. Z.H. M.A. A.A. N.W. M.M. L.S.G. S.E. M.K. G.M. T.S. Z.Z. K.M. Y.Z. K.C. V.C. and T.S.-S.; Data Curation, A.A.A. C.Y. Z.H. and M.A.; Methodology and Formal Analysis and Visualization, A.A.A. C.Y. Z.H. and A.A.; Writing – Original Draft, A.A.A. C.Y. Z.H. M.A. and A.A.; Writing – Review & Editing, A.A.A. C.Y. and Z.H.; Resources (Clinical Samples), M.M. S.Damato, S.Dhar, V.R. R.G.C. H.S. D.M.-P. and S.J. A.A.A. C.Y. and Z.H. filed a patent application for the use of the 52-gene panel for predicting the prognosis in ovarian cancer.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/2/10
Y1 - 2020/2/10
N2 - The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC. Using single-cell RNA sequencing, Hu et al. identify six subtypes of fallopian tube epithelium (FTE) cells in normal human fallopian tube tissues. The FTE cellular subtypes reveal intra-tumoral heterogeneity in serous ovarian cancer (SOC) and define SOC subtypes that correlate with patient prognosis.
AB - The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC. Using single-cell RNA sequencing, Hu et al. identify six subtypes of fallopian tube epithelium (FTE) cells in normal human fallopian tube tissues. The FTE cellular subtypes reveal intra-tumoral heterogeneity in serous ovarian cancer (SOC) and define SOC subtypes that correlate with patient prognosis.
KW - fallopian tube
KW - non-genetic heterogeneity
KW - ovarian cancer
KW - single-cell RNA sequencing
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U2 - 10.1016/j.ccell.2020.01.003
DO - 10.1016/j.ccell.2020.01.003
M3 - Article
C2 - 32049047
AN - SCOPUS:85078859150
SN - 1535-6108
VL - 37
SP - 226-242.e7
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -
