Genome-scale functional mapping of the mammalian whole brain with in vivo Perturb-seq
Shi, T.; Korshunova, M.; Kim, S.; DeTomaso, D.; Zheng, X.; Vishvanath, L.; Nyasulu, T.; Huynh, N.; Sun, A.; Thompson et al.
Functional genomics studies have provided critical insights into cell type-specific gene regulatory programs, but to date most have been conducted in wild-type tissues or cell cultures. Here, we present a gene expression functional atlas across the mouse brain. We use an enhanced in vivo Perturb-seq platform to analyze transcriptome-wide responses to loss of 1,947 disease-associated genes, profiling over 7.7 million cells spanning major brain regions and neuronal populations. We find striking cell-type-specific essentiality and transcriptional programs and show that closely related disease genes such as two NMDA receptor subunits can drive opposing transcriptional programs. Together, this work reveals insights into the genetics and mechanisms of neurodevelopmental, psychiatric, and neurodegenerative diseases in vivo, paving the way for the design of future genetic medicine.
A 7.7-million-cell brain heist where 1,947 disease genes get CRISPR-mugged in living mice, revealing cell-type-specific plot twists—like NMDA subunits throwing opposing transcriptional tantrums—while turning the whole mouse brain into a living "virtual cell" atlas for neuro quirks.
Shared by neurotech researcher Xin Jin (@xinjin) with strong engagement from the Perturb-seq and neuroscience communities for its scale and disease-gene insights; highlighted by PerturbAI launch coverage as a major in vivo atlas
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