Center for Cancer Immunotherapy, La Jolla Institute for Immunology, La Jolla, CA, USA.
Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cell Rep. 2021 Apr 13;35(2):108978. doi: 10.1016/j.celrep.2021.108978.
The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3 intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.
人类输卵管是大多数高级别浆液性“卵巢”癌（HGSCs）的起源细胞，但它的细胞组成，特别是上皮成分，特征描述较差。我们对来自 12 个原发性输卵管标本的大约 53000 个单个细胞进行单细胞转录组谱分析，以绘制其主要细胞类型图。我们确定了 10 个具有不同转录程序的上皮亚群。基于转录特征，我们重建了一条轨迹，即分泌细胞通过 RUNX3 中间产物分化为纤毛细胞。对高级别 HGSC 的计算反卷积将“早期分泌”群体鉴定为大多数 HGSC 的可能前体状态。其特征包含上皮和间充质特征，并且在间充质型 HGSC 中富集（p = 6.7×10），这是一组已知预后特别差的肿瘤。这份来自无癌女性的人类输卵管的细胞和分子汇编有望促进我们对输卵管上皮肿瘤发生的最早阶段的理解。
