Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies.
Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies.
复制标题
DOI：
10.3389/fgene.2023.1241834
复制
发表时间：
2023
影响因子：
3.7
通讯作者：
Zhang, Zheng-Yun
中科院分区：
文献类型：
--
作者：
Zhou, Zun-Qiang;Zhang, Yi;Xu, Zi-Yang;Tang, Xiao-Li;Chen, Xiao-Hua;Guan, Jiao;Zhang, Zheng-Yun
背景：胆管细胞癌具有显著的细胞异质性和复杂的细胞间通讯，这是导致其进展和治疗耐药的原因之一。因此，解开这种复杂性对于开发有效的治疗方法至关重要。方法：我们采用单细胞RNA测序技术(scRNA-seq)研究了2例胆管细胞癌及其癌旁正常组织的细胞异质性和细胞间通讯。鉴定了不同的细胞类型，并进行了基因本体论分析以确定丰富的途径。此外，使用计算框架CellChat分析了细胞间的通信。此外，我们对T细胞和成纤维细胞进行了亚群分析。结果：scRNA-seq分析显示胆管癌细胞具有明显的细胞团和不同的细胞成分。CellChat分析强调了肿瘤内成纤维细胞发出的放大信号，表明它们在肿瘤微环境中发挥着关键作用。此外，T细胞亚群分析显示肿瘤内有积极的免疫反应和新的肿瘤特异性T细胞克隆类型，这表明靶向免疫治疗的范围。此外，成纤维细胞亚群分析显示了不同的功能状态，并强调了激活的成纤维细胞在塑造细胞间通讯方面的作用，特别是通过CD99和FN1信号。结论：我们的研究结果揭示了胆管细胞癌复杂的细胞异质性和动态的细胞间通讯，为疾病进展和潜在的治疗策略提供了有价值的见解。
Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments. Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts. Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling. Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies.
登录
查看更多内容
影响因子：
2.6
作者：
Ali, Atham;Vaikari, Vijaya Pooja;Alachkar, Houda
通讯作者：
Alachkar, Houda
影响因子：
16.6
作者：
Song G;Shi Y;Meng L;Ma J;Huang S;Zhang J;Wu Y;Li J;Lin Y;Yang S;Rao D;Cheng Y;Lin J;Ji S;Liu Y;Jiang S;Wang X;Zhang S;Ke A;Wang X;Cao Y;Ji Y;Zhou J;Fan J;Zhang X;Xi R;Gao Q
通讯作者：
Gao Q
通过单细胞 RNA 测序辅助多组学分析发现肝内胆管癌的分子亚组。
影响因子：
10.1
作者：
Bao, Xuanwen;Li, Qiong;Ruan, Jian
通讯作者：
Ruan, Jian
影响因子：
46.9
作者：
Butler A;Hoffman P;Smibert P;Papalexi E;Satija R
通讯作者：
Satija R
影响因子：
17.1
作者：
Chung SS;Eng WS;Hu W;Khalaj M;Garrett-Bakelman FE;Tavakkoli M;Levine RL;Carroll M;Klimek VM;Melnick AM;Park CY
通讯作者：
Park CY