Single-cell analysis reveals that TCF7L2 facilitates the progression of ccRCC via tumor-associated macrophages

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-10-02 DOI:10.1016/j.cellsig.2024.111453

Fengran Guo , Yilong Gao , Pengfei Zhou , Hu Wang , Ziyang Ma , Xiaowei Wang , Xin Wang , Xiaojuan Feng , Yaxuan Wang , Zhenwei Han

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Abstract

Background

Tumor-associated macrophages (TAMs) play an important role in the recurrence and progression of clear cell renal cell carcinoma (ccRCC). However, the specified mechanism has not been elucidated.

Methods

Single-cell and transcriptome analysis were applied to characterize the heterogeneity of TAMs. SCENIC would infer regulators of different subsets of TAMs. The CellChat algorithm was used to infer macrophage-tumor interaction networks, whereas pseudo-time traces were used to parse cell evolution and dynamics.

Results

In this study, single-cell transcriptomic data of ccRCC were analyzed. Notably, the macrophages were clustered to select the cluster with a tendency toward M2-type TAM, which has an impact on the occurrence and metastasis of ccRCC. This macrophage cluster was defined as “TAM2”. And this study revealed that TCF7L2 as a potential transcription factor regulating TAM2 transcriptional heterogeneity and differentiation. Pseudotime traces showed TCF7L2 trajectories during TAM2 cell cluster development. In addition, the results of cell interaction showed that TAM2 had the highest number and strength of interactions with cancer cells and endothelial cells. In vitro experiments, this study found that TCF7L2 was highly expressed in TAMs and promoted the polarization of macrophages to M2-type macrophages. And then overexpression of TCF7L2 in macrophages markedly promoted ccRCC invasion and proliferation.

Conclusion

TCF7L2 could play a key role in the progression of ccRCC via enhancing TAMs recruitment and M2-type polarization.

Abstract Image

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单细胞分析表明，TCF7L2 通过肿瘤相关巨噬细胞促进了 ccRCC 的进展。

背景：肿瘤相关巨噬细胞（TAMs）在透明细胞肾细胞癌（ccRCC）的复发和进展中发挥着重要作用。然而，其具体机制尚未阐明：方法：应用单细胞和转录组分析来描述TAMs的异质性。SCENIC 将推断 TAMs 不同亚群的调节因子。CellChat算法用于推断巨噬细胞与肿瘤的相互作用网络，而伪时间轨迹则用于解析细胞的进化和动态：本研究分析了ccRCC的单细胞数据。结果：该研究分析了ccRCC的单细胞数据。值得注意的是，对巨噬细胞进行了聚类，筛选出倾向于M2型TAM的集群，这对ccRCC的发生和转移有影响。该巨噬细胞群被定义为 "TAM2"。这项研究发现，TCF7L2 是调控 TAM2 转录异质性和分化的潜在转录因子。伪时间轨迹显示了TCF7L2在TAM2细胞簇发育过程中的轨迹。此外，细胞相互作用的结果表明，TAM2 与癌细胞和内皮细胞相互作用的次数和强度最高。在体外实验中，本研究发现 TCF7L2 在 TAMs 中高表达，并能促进巨噬细胞极化为 M2 型巨噬细胞。结论：TCF7L2可在ccRCC中发挥重要作用：结论：TCF7L2可通过增强TAMs招募和M2型极化在ccRCC的进展中发挥关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.