Mapping how different brain cell types and ages affect neuron vulnerability using gene-silencing screens in mice

A consensus set of 269 neuronal core essential genes was identified through systematic gene function profiling in the mouse brain.

• A scalable, cell-type-resolved CRISPR interference platform was developed for gene function profiling in vivo.
• Genome-wide screens were conducted across four neuronal populations at three time points from youth to aging.
• Cell-type-specific genetic vulnerabilities were identified, with differences in dependencies for certain genes between excitatory and inhibitory neurons.
• Aging-specific dependencies were found to be enriched in mitochondrial and translational pathways, correlating with transcriptional changes observed in the aging human brain.
• The CRISPRinvivo data portal has been established as a community resource for in vivo screening.

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