Li Chunbo, Guo Luopei, Li Shengli, Hua Keqin
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
Mol Ther Nucleic Acids. 2021 Apr 2;24:682-694. doi: 10.1016/j.omtn.2021.03.017. eCollection 2021 Jun 4.
Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome analysis (single-cell RNA sequencing [scRNA-seq]) of CC cells and microenvironment has not been conducted. In this study, a total of 20,938 cells from CC and adjacent normal tissues were examined by scRNA-seq. We identified four tumor cell subpopulations in tumor cells, which had specific signature genes with different biological functions and presented different prognoses. Among them, we identified a subset of cancer stem cells (CSCs) that was related to the developmental hierarchy of tumor progression. Then, we compared the expressive differences between tumor-derived endothelial cells (TECs) and normal ECs (NECs) and revealed higher expression of several metabolism-related genes in TECs. Then, we explored the potential biological function of ECs in vascularization and found several marker genes, which played a prior role in connections between cancer cells and ECs. Our findings provide valuable resources for deciphering the intra-tumoral heterogeneity of CC and uncover the developmental procedure of ECs, which paves the way for CC therapy.
宫颈癌（CC）是妇科恶性肿瘤中第四大致死原因。尽管对CC的病因已进行了广泛研究，但其确切发病机制仍不明确。最近，单细胞技术在探索各种肿瘤细胞内的肿瘤异质性方面显示出优势。然而，尚未对CC细胞和微环境进行单细胞转录组分析（单细胞RNA测序[scRNA-seq]）。在本研究中，通过scRNA-seq对来自CC组织和相邻正常组织的总共20938个细胞进行了检测。我们在肿瘤细胞中鉴定出四个肿瘤细胞亚群，它们具有不同生物学功能的特异性标志基因，并呈现出不同的预后。其中，我们鉴定出了一组与肿瘤进展发育层次相关的癌症干细胞（CSCs）。然后，我们比较了肿瘤来源的内皮细胞（TECs）和正常内皮细胞（NECs）之间的表达差异，发现TECs中几个与代谢相关的基因表达较高。接着，我们探讨了内皮细胞在血管生成中的潜在生物学功能，并发现了几个在癌细胞与内皮细胞连接中起重要作用的标记基因。我们的研究结果为解读CC的肿瘤内异质性提供了宝贵资源，并揭示了内皮细胞的发育过程，为CC治疗铺平了道路。
