Evidence map›Paper›PMID 32004439›Full record

ArticleNeuron2020

Genome-wide In Vivo CNS Screening Identifies Genes that Modify CNS Neuronal Survival and mHTT Toxicity.

Mary H Wertz, Mollie R Mitchem, S Sebastian Pineda, Lea J Hachigian, Hyeseung Lee, Vanessa Lau, Alex Powers, Ruth Kulicke, Gurrein K Madan, Medina Colic and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
10.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Properties and Application of Pseudotyped Lentiviral Vectors.Methods in molecular biology (Clifton, N.J.) · 2026
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  9. Review
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  11. Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 1 country.

Mary H WertzPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mollie R MitchemPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
S Sebastian PinedaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA.
Lea J HachigianDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hyeseung LeePicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vanessa LauPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alex PowersPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ruth KulickePicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Gurrein K MadanDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Medina ColicUniversity of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Martine TherrienPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Amanda VernonDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Victoria F Beja-GlasserDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Mudra HegdeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Fan GaoPicower Institute for Learning and Memory, Cambridge, MA 02139, USA; Bioinformatics Resource Center in the Beckman Institute at Caltech, Pasadena, CA 91125, USA.
Manolis KellisBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139, USA.
Traver HartUniversity of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John G DoenchBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Myriam HeimanDepartment of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mheiman@mit.edu.
Broad Institute · USThe University of Texas MD Anderson Cancer Center · USCalifornia Institute of Technology · USMcGovern Institute for Brain Research · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
High-content microscopy platform for multiplex perturbation/multiplex readout studiesR35GM130119 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Traver Hart · 2018 to 2026
$3.9M
Development of SLIC, a methodology for synthetic lethal screening in the CNSR01NS085880 · NINDS · BROAD INSTITUTE, INC. · PI HEIMAN, MYRIAM · 2013 to 2016
$1.4M
Supplement to Neurobiological Engineering Training ProgramT32EB019940 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JASANOFF, ALAN · 2015 to 2025
$1.4M
NCI NIH HHS P30 CA016672NIBIB NIH HHS T32 EB019940NIGMS NIH HHS R35 GM130119NINDS NIH HHS R01 NS085880
6 · The paper itself

Abstract

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 short hairpin RNA (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.

Indexed as

AnimalsBehavior, AnimalCell SurvivalCRISPR-Cas SystemsGene Knockdown TechniquesGene LibraryGenes, EssentialHuntingtin ProteinHuntington DiseaseMiceMice, TransgenicNeostriatumNeuronsNM23 Nucleoside Diphosphate KinasesNucleoside Diphosphate Kinase DProtein AggregatesDRD2 protein, mouseHTT protein, humanHuntingtin ProteinNM23 Nucleoside Diphosphate KinasesNme1 protein, mouseNme3 protein, mouseNme4 protein, mouseNucleoside Diphosphate Kinase DProtein AggregatesReceptors, Dopamine D2RNA, Guide, CRISPR-Cas SystemsRNA, Small Interferinggenome-wide screeningHuntington’s diseaseneuronal essential genesNme1

Identifiers

PMID32004439
PMCPMC7181458
OpenAlexW3004187300

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.