RNA sequencing, transcriptomic alternations in response to lysosomal damage

Lysosomes are the primary degradative organelles and play a pivotal role in maintaining cellular and tissue homeostasis. Lysosomal dysfunction is associated with various diseases, underscoring the crucial role of lysosomal integrity and its quality control in human health Lysosomes are susceptible to damage by many sources, both internal and external to the cell, which results in the permeabilization and rupture of lysosomal membranes. Crystals, amyloids, pathogens, lipids, lysosomal toxic drugs, and reactive oxygen species (ROS) are among the stressors that can damage lysosomal membranes. To comprehensively investigate the changes in gene expression caused by lysosomal damage, we performed transcriptome analysis and compared mRNA expression between RPE-1 cells treated with or without L-Leucyl-L-Leucine methyl ester (LLOMe), a well-characterized inducer of lysosomal damage, for 2 h.

溶酶体（Lysosomes）是细胞内主要的降解细胞器，在维持细胞与组织稳态方面发挥关键作用。溶酶体功能异常与多种疾病密切相关，凸显了溶酶体完整性及其质量调控对人类健康的重要意义。溶酶体易受细胞内外多种因素的损伤，进而导致溶酶体膜通透性增加与破裂。晶体、淀粉样蛋白、病原体、脂质、溶酶体毒性药物以及活性氧（reactive oxygen species, ROS）均属于可损伤溶酶体膜的应激源。为全面解析溶酶体损伤所诱导的基因表达变化，本研究对RPE-1细胞开展转录组分析（transcriptome analysis），对比了经2小时处理的、经已被充分表征的溶酶体损伤诱导剂L-亮氨酰-L-亮氨酸甲酯（L-Leucyl-L-Leucine methyl ester, LLOMe）处理与未处理的细胞的mRNA表达水平。