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异质和新型的转录表达在单细胞患者衍生的透明细胞脏细胞癌器官的单细胞

Tülay Karakulak^1,2,3, Natalia Zajac^3,4, Hella Anna Bolck^2,5

¹Department of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.

Genome research

|March 19, 2025

概括

拼接失调在清细胞细胞癌 (ccRCC) 中很常见. 这项研究揭示了ccRCC患者衍生器官中广泛的新型转录和细胞特异的拼接模式,突出了转录组复杂性.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

剪接变化是癌症的标志,影响基因表达和蛋白质异型.
清细胞细胞癌 (ccRCC) 呈现出复杂的分子特征,这有助于其侵略性.

研究的目的:

为了全面地描述ccRCC的转录学景观,使用全长转录序列.
在患者衍生有机细胞 (PDO) 中识别新型转录和替代拼接事件.
调查ccRCC中拼接失调的异质性.

主要方法:

在PacBio平台上使用多重排列测序 (MAS-seq) 协议.
从2599个单个ccRCC PDO单元格中测序的全长转录.
应用了严格的过标准来识别新的转录,并分析了转录切换事件.

主要成果:

鉴定了31531个新型转录 (36.6%的总检测),其中许多具有细胞特异性表达.
在ccRCC细胞中常见的新型转录与缺氧和氧化酸化等关键途径有关.
超过50%的新型转录有预测的完整的蛋白质编码开放的读取框架;尼古丁胺N-甲基转移酶的新型转录得到了验证.

结论:

在单细胞水平上,ccRCC表现出显著的拼接异质性.
这项研究揭示了ccRCC中复杂的转录结构,包括许多新的转录.
研究结果提供了关于ccRCC攻击性的分子基础的见解,并为未来研究提供了潜在的目标.

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