Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube.
Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube.
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DOI：
10.1016/j.celrep.2021.108978
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发表时间：
2021-04-13
期刊：
影响因子：
8.8
通讯作者：
Lawrenson, Kate
中科院分区：
文献类型：
--
作者：
Dinh, Huy Q.;Lin, Xianzhi;Abbasi, Forough;Nameki, Robbin;Haro, Marcela;Olingy, Claire E.;Chang, Heidi;Hernandez, Lourdes;Gayther, Simon A.;Wright, Kelly N.;Aspuria, Paul-Joseph;Karlan, Beth Y.;Corona, Rosario, I;Li, Andrew;Rimel, B. J.;Siedhoff, Matthew T.;Medeiros, Fabiola;Lawrenson, Kate
人输卵管窝藏大多数高级别浆液性“卵巢”癌（HGSC）的起源细胞，但其细胞组成，特别是上皮成分的特征很差。我们对来自12个原发性输卵管标本的约53，000个单个细胞进行单细胞转录组学分析，以绘制其主要细胞类型。我们确定了10个上皮细胞亚群与不同的转录程序。基于转录签名，我们重建了一个轨迹，分泌细胞分化成纤毛细胞通过RUNX 3 high中间。晚期HGSC的计算解卷积将“早期分泌”群体鉴定为大多数HGSC的可能前体状态。其特征包括上皮和间充质特征，并富含间充质型HGSC（p = 6.7 × 10 - 27），已知这类HGSC的预后特别差。这一无癌妇女输卵管的细胞和分子概要有望促进我们对输卵管上皮瘤形成早期阶段的理解。使用来自人输卵管的约53，000个细胞的单细胞转录组学分析，Dinh等人将SOX 17鉴定为输卵管上皮中的关键因子，并构建了涉及RUNX 3+中间体的分化轨迹。早期分泌性上皮细胞被认为是高级别浆液性卵巢癌的起源细胞。
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 RUNX3high 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 × 10−27), 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. Using single-cell transcriptomic profiling of around 53,000 cells from human fallopian tubes, Dinh et al. identify SOX17 as a critical factor in fallopian epithelia and construct a differentiation trajectory involving a RUNX3+ intermediate. Early secretory epithelial cells are revealed to be a likely cell of origin for high-grade serous “ovarian” carcinomas.
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影响因子：
12.4
作者：
Haas, Andrew R.;Tanyi, Janos L.;Beatty, Gregory L.
通讯作者：
Beatty, Gregory L.
影响因子：
64.8
作者：
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通讯作者：
Shendure, Jay
影响因子：
46.9
作者：
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通讯作者：
Newell, Evan W.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus