Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC.
Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC.
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DOI：
10.1016/j.omtn.2021.03.017
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Hua K
中科院分区：
文献类型：
--
作者：
Li C;Guo L;Li S;Hua K
宫颈癌（CC）是妇科恶性肿瘤中第四大死亡原因。虽然CC的病因已被广泛研究，CC的确切发病机制仍然不完整。最近，单细胞技术在探索各种肿瘤细胞之间的肿瘤内多样化方面表现出优势。然而，尚未进行CC细胞和微环境的单细胞转录组分析（单细胞RNA测序[scRNA-seq]）。在这项研究中，通过scRNA-seq检查了来自CC和邻近正常组织的总共20，938个细胞。我们在肿瘤细胞中发现了四个肿瘤细胞亚群，它们具有不同生物学功能的特异性标记基因，并呈现不同的表达。其中，我们确定了一个癌症干细胞（CSC）的子集，与肿瘤进展的发育层次有关。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，并揭示了TECs中几个代谢相关基因的高表达。然后，我们探索了内皮细胞在血管形成中的潜在生物学功能，发现了几个在癌细胞与内皮细胞之间的连接中起优先作用的标记基因。我们的研究结果提供了宝贵的资源，破译肿瘤内的异质性CC和揭示EC的发展过程，这为CC的治疗铺平了道路。本研究在单细胞分辨率下描述了宫颈癌（CC）的肿瘤内异质性和发展过程，并为CC的治疗策略提供了有价值的资源。
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. This study characterizes intra-tumor heterogeneity and developmental procedures of cervical cancer (CC) at single-cell resolution and provides valuable resources for therapeutic strategies of CC.
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