Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube

• DOI: 10.1016/j.celrep.2021.108978
• Publication Date: 2021-04-15T14:24:10Z
• Authors: Huy Q. Dinh; Xianzhi Lin; Forough Abbasi; Robbin Nameki; Marcela Haro; Claire E. Olingy; Heidi Chang; Lourdes Hernandez; Simon A. Gayther; Kelly N. Wright; Paul-Joseph Aspuria; Beth Y. Karlan; Rosario I. Corona; Andrew Li; B.J. Rimel; Matthew T. Siedhoff; Fabiola Medeiros; Kate Lawrenson
• Keywords: Fallopian tube

The human fallopian tube harbors the cell of origin for majority high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling around 53,000 individual cells from 12 primary specimens to map their major types. identify 10 subpopulations with diverse transcriptional programs. Based on signatures, we reconstruct a trajectory whereby secretory differentiate into ciliated via RUNX3high intermediate. Computational deconvolution advanced HGSCs identifies "early secretory" population as likely precursor state HGSCs. Its signature comprises both and mesenchymal features enriched in mesenchymal-type (p = 6.7 × 10−27), group known have poor prognoses. This molecular compendium cancer-free women expected advance our understanding earliest stages neoplasia.