瘤微环境显示出由纤维细胞主导的细胞细胞相互作用的层次结构
Shimrit Mayer1, Tomer Milo2, Achinoam Isaacson1
1Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot, Israel.
Nature communications
|September 19, 2023
概括
研究人员通过识别关键细胞相互作用电路来简化复杂的瘤微环境 (TME). 他们发现了一个分层网络,癌症相关纤维细胞 (CAFs) 影响瘤相关巨细胞 (TAMs),揭示了潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 系统生物学 系统生物学
- 细胞生物学 细胞生物学
背景情况:
- 瘤微环境 (TME) 是由与癌细胞相互作用的非恶性细胞组成的复杂生态系统,显著影响癌症的进展.
- 了解复杂的TME需要创新的方法来剖析细胞交叉通话及其对瘤生物学的影响.
研究的目的:
- 开发一个实验数学框架,通过将TME分解成基本的相互作用细胞电路来简化TME.
- 识别和描述TME中的关键细胞相互作用动机,特别是在女性乳腺癌中.
主要方法:
- 应用单细胞RNA测序方法来分析女性乳腺癌数据.
- 开发了一种实验数学模型,将TME分解为相互作用的细胞电路.
- 利用体外共同培养系统来隔离和研究特定的双细胞电路模式,分析细胞动态和转录组.
主要成果:
- 确定了TME内部的层次相互作用网络,癌症相关纤维细胞 (CAFs) 主要分泌因子到瘤相关巨细胞 (TAMs).
- 发现的重复电路图案构成了TME网络的基础.
- 隔离并描述了最强的双细胞电路基因 (CAF-TAM),证实了体内相互作用层次,并通过其受体CMKLR1.1识别了RARRES2作为CAF-TAM相互作用的关键媒介.
结论:
- 通过识别和分析小的基本电池电路,可以有效地简化TME的复杂性.
- 这种基于电路的方法促进了对联体受体相互作用及其在TME中的功能后果的研究.
- 这些发现为开发新的策略提供了基础,以调节TME相互作用以获得治疗益处.
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