与胰岛素信号相关的细胞命运通过cis-regulatory元素激活促进非功能性垂体淋巴腺瘤的瘤侵入性
Hongwei Liu1,2,3, Zhouyang Pan1,2,3, Qi Yang1,2,3
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
非功能性垂体淋巴腺腺瘤 (NFGA) 通过胰岛素信号传递变得具有侵入性. 针对胰岛素耐药性为侵入性NFGA提供了一个新的治疗策略,改善了患者的治疗结果.
科学领域:
- 内分泌学 在内分泌学.
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 非功能性垂体淋巴腺腺瘤 (NFGA) 是最常见的垂体瘤类型.
- NFGA通常会变得侵入性和耐治疗.
- 了解NFGA的侵入性机制对于开发有效疗法至关重要.
研究的目的:
- 研究NFGA入侵中的细胞异质性.
- 确定NFGA侵入性的分子驱动因素.
- 评估胰岛素信号在NFGA瘤进展中的作用.
主要方法:
- 综合单细胞RNA测序 (scRNA-seq) 和单细胞ATAC测序 (scATAC-seq) 来自NFGA患者.
- 分析了210名患者和初级细胞系的独立队列.
- 进行了体外测试和cis-co-accessible网络分析.
主要成果:
- 在NFGA中确定了五种细胞状态和三种独特的细胞命运,具有表观遗传异质性.
- 发现胰岛素信号作为瘤侵入性的驱动因素,侵入性NFGA显示胰岛素耐药性.
- 在侵入性NFGA中观察到与胰岛素信号相关的 cis-regulatory元素 (CREs) 的改变色素相互作用.
结论:
- 通过CREs激活胰岛素信号驱动NFGA中的侵入性细胞命运.
- 增加的胰岛素抵抗与NFGA的侵入性有关.
- 准胰岛素信号传递为侵入性NFGA提供了潜在的治疗途径.
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