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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
Single-cell profiling of Nme1 overexpressing spiny projection neurons in R62 mouse model of HD
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Contributor(s) |
Pineda SS, Heiman M |
Citation(s) |
32004439 |
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Submission date |
Dec 11, 2019 |
Last update date |
Feb 03, 2020 |
Contact name |
Myriam Heiman |
E-mail(s) |
mheiman@mit.edu
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Organization name |
Massachusetts Institute of Technology
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Department |
Brain and Cognitive Sciences
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Lab |
Heiman
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Street address |
77 Massachusetts Ave., Bldg 46-4285
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City |
Cambridge |
State/province |
Massachusetts |
ZIP/Postal code |
02139 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (20)
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GSM4214745 |
Spiny projection neurons, NonCar_CtlOX, rep1 |
GSM4214746 |
Spiny projection neurons, NonCar_CtlOX, rep2 |
GSM4214747 |
Spiny projection neurons, NonCar_CtlOX, rep3 |
GSM4214748 |
Spiny projection neurons, NonCar_CtlOX, rep4 |
GSM4214749 |
Spiny projection neurons, NonCar_CtlOX, rep5 |
GSM4214750 |
Spiny projection neurons, NonCar_Nme1OX, rep1 |
GSM4214751 |
Spiny projection neurons, NonCar_Nme1OX, rep2 |
GSM4214752 |
Spiny projection neurons, NonCar_Nme1OX, rep3 |
GSM4214753 |
Spiny projection neurons, NonCar_Nme1OX, rep4 |
GSM4214754 |
Spiny projection neurons, NonCar_Nme1OX, rep5 |
GSM4214755 |
Spiny projection neurons, R62Hemi_CtlOX, rep1 |
GSM4214756 |
Spiny projection neurons, R62Hemi_CtlOX, rep2 |
GSM4214757 |
Spiny projection neurons, R62Hemi_CtlOX, rep3 |
GSM4214758 |
Spiny projection neurons, R62Hemi_CtlOX, rep4 |
GSM4214759 |
Spiny projection neurons, R62Hemi_CtlOX, rep5 |
GSM4214760 |
Spiny projection neurons, R62Hemi_Nme1OX, rep1 |
GSM4214761 |
Spiny projection neurons, R62Hemi_Nme1OX, rep2 |
GSM4214762 |
Spiny projection neurons, R62Hemi_Nme1OX, rep3 |
GSM4214763 |
Spiny projection neurons, R62Hemi_Nme1OX, rep4 |
GSM4214764 |
Spiny projection neurons, R62Hemi_Nme1OX, rep5 |
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Relations |
BioProject |
PRJNA594969 |
SRA |
SRP236888 |
Supplementary file |
Size |
Download |
File type/resource |
GSE141856_RAW.tar |
985.9 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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