Imbalanced Unfolded Protein Response Signaling Contributes to 1-Deoxysphingolipid Retinal Toxicity

1-deoxysphinganine accumulation is associated with retinal toxicity. We used single nucelus and bulk sequencing to profile transcriptional remodeling following treatment with 1-dexoysphnganine in human iPSC-derived retinal organoids. Overall design: Human iPSC-derived retinal organoids were incubated with 1-dSA for either 2 days, 3 days or 4 days. At four days, organoids were treated with 1-dSA in the presence or absence of the ISRIB or AA147.

1-脱氧神经鞘氨醇（1-deoxysphinganine）的蓄积与视网膜毒性密切相关。本研究采用单细胞核测序与批量测序技术，对人类诱导多能干细胞（induced pluripotent stem cell, iPSC）来源的视网膜类器官经1-脱氧神经鞘氨醇处理后的转录组重塑特征进行了解析。总体实验设计：将人类诱导多能干细胞来源的视网膜类器官置于含1-dSA的培养基中分别培养2天、3天或4天；在培养至第4天时，分别在添加或不添加ISRIB与AA147的条件下用1-脱氧神经鞘氨醇处理类器官。