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单细胞转录组谱分析鉴定出未成熟卵巢畸胎瘤中潜在的与转移相关的 UBE2C+ 细胞簇。

Single-cell transcriptional profiling identifies a cluster of potential metastasis-associated UBE2C+ cells in immature ovarian teratoma.

机构信息

Department of Pediatric Surgery, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Birth Defect, Shanghai, 201102, China.

Department of Pediatric Surgery, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Birth Defect, Shanghai, 201102, China.

出版信息

Biochem Biophys Res Commun. 2020 Jul 30;528(3):567-573. doi: 10.1016/j.bbrc.2020.05.144. Epub 2020 Jun 3.

Abstract

To dissect the disease heterogeneity and identify the underlying cellular and molecular events related to metastasis of immature ovarian teratoma in children, single-cell RNA sequencing was performed for a 2-year-old patient with liver metastases from immature ovarian teratoma. A total of 5976 cells were obtained for further analysis, with a median unique molecular identifier count of 6011 per cell and a median number of 1741 genes detected per cell. Fourteen clusters were recognized, with the main lineages comprising epithelial cells, macrophages, fibroblasts, glial cells, and dendritic cells. Ten subclusters of epithelial cells were further defined, originating from the urinary tract, esophagus, bronchus, lung, skin, and gastrointestinal tract. An undefined UBE2C + population in an active state of proliferation was also identified and its biological processes were related to meiosis and maturation of oocytes. Pseudotime analysis revealed different distributions of epithelial cells in the development trajectory. In conclusion, a cluster of UBE2C + epithelial cells in an active state of proliferation was identified in an immature ovarian teratoma in a child, and may contribute to metastasis by regulating epithelial-mesenchymal transition. These findings help toward understanding the origin of the malignant behaviors, offer a potential biomarker for early determination of the tumor nature, and provide new ideas for the therapy of immature ovarian teratoma in children.

摘要

为了解析疾病异质性并鉴定与儿童未成熟卵巢畸胎瘤转移相关的潜在细胞和分子事件,对 1 例 2 岁肝转移未成熟卵巢畸胎瘤患儿进行了单细胞 RNA 测序。共获得 5976 个细胞进行进一步分析,每个细胞的中位数独特分子标识符计数为 6011,每个细胞检测到的中位数基因数为 1741。识别出 14 个簇,主要谱系包括上皮细胞、巨噬细胞、成纤维细胞、神经胶质细胞和树突状细胞。进一步定义了 10 个上皮细胞亚簇,来源于泌尿道、食管、支气管、肺、皮肤和胃肠道。还鉴定了一个处于增殖活跃状态的未定义 UBE2C+群体,其生物学过程与卵母细胞的减数分裂和成熟有关。拟时分析显示上皮细胞在发育轨迹中的不同分布。总之,在儿童未成熟卵巢畸胎瘤中鉴定到处于增殖活跃状态的 UBE2C+上皮细胞簇,可能通过调节上皮-间充质转化促进转移。这些发现有助于了解恶性行为的起源,为早期确定肿瘤性质提供潜在的生物标志物,并为儿童未成熟卵巢畸胎瘤的治疗提供新的思路。

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