Genome-wide CRISPRi/a screens in human neurons link lipid imbalance to ferroptosis
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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http://data.iscr.ac.cn/Article?id=def73da5e5e82c146a500353f8217170
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资源简介：
Neurons are unique among all human cell types in their high energy demand, long lifespans and rich lipid contents. As such, neurons exhibit unique vulnerability to oxidative stress caused by redox imbalance in aging and neurodegenerative diseases (NDDs). To systematically identify regulators of neuronal survival under oxidative stress and regulators of neuronal redox homeostasis, we conducted multiple survival- and FACS-based genome-wide screens in human iPSC-derived neurons, using our functional genomics toolkit including a previously established CRISPRi approach and a newly developed CRISPRa approach. So far, these are the first genome-wide screens in human neurons. Our results revealed that inhibiting glycosphingolipids (GSLs) degradation by depletion of prosaposin (PSAP) drives the formation of lipofuscins in neurons which leads to iron accumulation and strongly induces ROS production that oxidizing lipids and leads to neuronal ferroptosis under oxidative stress. We also conducted single cell CROP-seq screens that revealed transcriptomic signatures of NDD-associated genes. These datasets are freely available through our open-access database CRISPRbrain.
提供机构：
University of California, San Francisco
创建时间：
2022-02-20
