Project description:Understanding the complex interplay between gene expression and neuronal activity is crucial for unraveling the molecular mechanisms underlying cognitive function and neurological disorders. Here, we developed pooled screens for neuronal activity, using CRISPR interference (CRISPRi) and the fluorescent calcium integrator CaMPARI2. Using this screening method, we evaluated 1343 genes for their effect on excitability in human iPSC-derived neurons, revealing potential links to neurodegenerative and neurodevelopmental disorders. These genes include known regulators of neuronal excitability, such as TARPs and ion channels, as well as genes associated with autism spectrum disorder and Alzheimer's disease not previously described to affect neuronal excitability. This CRISPRi-based screening platform offers a versatile tool to uncover molecular mechanisms controlling neuronal activity in health and disease.
Project description:Understanding the complex interplay between gene expression and neuronal activity is crucial for unraveling the molecular mechanisms underlying cognitive function and neurological disorders. Here, we developed pooled screens for neuronal activity, using CRISPR interference (CRISPRi) and the fluorescent calcium integrator CaMPARI2. Using this screening method, we evaluated 1343 genes for their effect on excitability in human iPSC-derived neurons, revealing potential links to neurodegenerative and neurodevelopmental disorders. These genes include known regulators of neuronal excitability, such as TARPs and ion channels, as well as genes associated with autism spectrum disorder and Alzheimer's disease not previously described to affect neuronal excitability. This CRISPRi-based screening platform offers a versatile tool to uncover molecular mechanisms controlling neuronal activity in health and disease.
Project description:This SuperSeries is composed of the following subset Series: GSE12019: Fine-scale mapping of copy-number alterations with massively parallel sequencing GSE13372: High-resolution mapping of copy-number alterations with massively parallel sequencing Refer to individual Series
Project description:Massively parallel reporter assays (MPRAs) have the potential to link differences in genome sequence, including genetic variants, to tissue-specific regulatory function. Whole-animal MPRA (WhAMPRA), where systemic intravenous AAV effectively transduces the plasmid MPRA library to mouse tissues. This technology simultaneously determines the transcriptional functions of hundreds of enhancers in vivo across multiple tissues
Project description:Massively parallel reporter assays (MPRAs) have the potential to link differences in genome sequence, including genetic variants, to tissue-specific regulatory function. Whole-animal MPRA (WhAMPRA), where systemic intravenous AAV effectively transduces the plasmid MPRA library to mouse tissues. This technology simultaneously determines the transcriptional functions of hundreds of enhancers in vivo across multiple tissues