Related Experiment Video
Updated: Jan 23, 2026
08:49
Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens
Published on: June 6, 2020
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Genome-wide screens identify core regulators of cell surface prion protein expression
Kathryn S Beauchemin1, Surachai Supattapone2,3
1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, 7200 Vail Building, Hanover, NH, 03755, USA.
Scientific Reports
|January 21, 2026
Summary
Researchers identified key genes controlling cell surface prion protein (PrPC) levels in neuronal cells using CRISPR screens. These findings offer potential therapeutic targets for prion and neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cell surface prion protein (PrPC) is crucial in prion disease pathogenesis.
- Understanding PrPC regulation is vital for developing therapeutic strategies.
Purpose of the Study:
- To identify regulators of cell surface PrPC expression in neuronal cells.
- To investigate cell-state-dependent regulation of PrPC.
Main Methods:
- Genome-wide CRISPR/Cas9 knockout screens were performed on CAD5 cells (neuronal origin).
- Screens were conducted in both undifferentiated and differentiated CAD5 cell states.
- Validated regulators were identified through pathway and gene overlap analysis.
Main Results:
- Identified 46 positive and 21 negative regulators in undifferentiated CAD5 cells.
- Identified 41 positive and 13 negative regulators in differentiated CAD5 cells.
- Found 23 core regulators shared across both cell states, enriched in GPI anchor biosynthesis pathways.
Conclusions:
- Cellular prion protein expression is regulated by distinct mechanisms dependent on neuronal cell state.
- Identified core and state-specific regulators provide insights into PrPC biology.
- These regulators represent potential therapeutic targets for prion and neurodegenerative diseases.
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