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大量和单细胞RNA-Seq数据的机器学习集成揭示了Cathepsin B作为流感中中央PANoptosis调节器

Bin Liu¹, Lin Zhu¹, Caijuan Zhang¹

¹State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100010, China.

International journal of molecular sciences

|September 13, 2025

概括

流感病毒感染导致过度的PANoptosis,细胞死亡过程导致肺损伤. 研究人员将cathepsin B (CTSB) 确定为该过程的关键调节剂,这表明CTSB是潜在的治疗标.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
病毒学病毒学

背景情况:

流感A病毒 (IAV) 感染会导致严重的肺损伤,原因是过度的PANoptosis,这是一个被编程的细胞死亡途径.
在IAV感染期间驱动PANoptosis的分子机制尚未完全理解.

研究的目的:

调查流感感染肺中的PANoptosis细胞异质性和转录动态.
在IAV感染期间识别PANoptosis的关键分子调节剂.

主要方法:

集成批量和单细胞RNA测序 (scRNA-seq) 数据.
使用计算算法 (AUCell,ssGSEA,AddModuleScore) 来量化PANoptosis活动.
使用机器学习 (SVM,RF,LASSO) 来识别调节基因.
在小鼠模型中进行了体内验证.

主要成果:

主要在巨细胞和中性粒细胞中观察到PANoptosis活性.
卡瑟普辛B (CTSB) 被确定为PANoptosis的中央调节者.
在体内研究证实了IAV感染小鼠的升高的PANoptosis标志物和CTSB表达.
CTSB可能促进NLRP3炎症酶激活和溶酶体功能障碍诱导的细胞死亡.

结论:

在IAV感染期间,CTSB是一个关键的调解者,它将溶酶体完整性与先天免疫驱动的肺损伤联系起来.
向CTSB可能提供一种治疗策略,以减轻流感相关的免疫病理.

关键词:

这就是PANoptosis.卡塞普辛B (CTSB) 是一种流感A型病毒感染者机器学习是机器学习.一个单细胞RNA测序.

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