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Series GSE141856 Query DataSets for GSE141856
Status Public on Jan 30, 2020
Title Genome-wide in vivo CNS Screening Identifies Genes that Modify CNS Neuronal Survival and mHTT Toxicity
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Unbiased in vivo genome-wide genetic screening is a powerful approach to elucidate new molecular mechanisms, but such screening has not been possible to perform in the mammalian central nervous system (CNS). Here we report the results of the first genome-wide genetic screens in the CNS using both shRNA and CRISPR libraries. Our screens identify many classes of CNS neuronal essential genes, and demonstrate that CNS neurons are particularly sensitive not only to perturbations to synaptic processes, but also autophagy, proteostasis, mRNA processing, and mitochondrial function. These results reveal a molecular logic for the common implication of these pathways across multiple neurodegenerative diseases. To further identify disease-relevant genetic modifiers, we applied our screening approach to two mouse models of Huntington’s disease (HD). Top mutant Huntingtin toxicity modifier genes included several Nme genes and several genes involved in methylation-dependent chromatin silencing and dopamine signaling, results that reveal new HD therapeutic target pathways.
Overall design Single-cell profiling of Nme1 overexpressing spiny projection neurons in R62 mouse model of HD
Contributor(s) Pineda SS, Heiman M
Citation(s) 32004439
Submission date Dec 11, 2019
Last update date Feb 03, 2020
Contact name Myriam Heiman
Organization name Massachusetts Institute of Technology
Department Brain and Cognitive Sciences
Lab Heiman
Street address 77 Massachusetts Ave., Bldg 46-4285
City Cambridge
State/province Massachusetts
ZIP/Postal code 02139
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (20)
GSM4214745 Spiny projection neurons, NonCar_CtlOX, rep1
GSM4214746 Spiny projection neurons, NonCar_CtlOX, rep2
GSM4214747 Spiny projection neurons, NonCar_CtlOX, rep3
BioProject PRJNA594969
SRA SRP236888

Download family Format
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Supplementary file Size Download File type/resource
GSE141856_RAW.tar 985.9 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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