Evidence map›Paper›PMID 29961565›Full record

ArticleBiological psychiatry2019

Endogenous Cell Type-Specific Disrupted in Schizophrenia 1 Interactomes Reveal Protein Networks Associated With Neurodevelopmental Disorders.

Brent Wilkinson, Oleg V Evgrafov, DongQing Zheng, Nicolas Hartel, James A Knowles, Nicholas A Graham, Justin K Ichida, Marcelo P Coba

Abstract read
In one paragraph

Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  4. Differential Association of theInternational journal of molecular sciences · 2025
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  10. Zebrafish as a model to investigate the CRH axis and interactions with DISC1.Current opinion in endocrine and metabolic research · 2022
    Review
  11. Mutations in DISC1 alter IPNeuronal signaling · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Brent WilkinsonZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
Oleg V EvgrafovDepartment of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York.
DongQing ZhengMork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California.
Nicolas HartelMork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California.
James A KnowlesDepartment of Cell Biology, SUNY Downstate Medical Center, Brooklyn, New York.
Nicholas A GrahamMork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California.
Justin K IchidaZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, California.
Marcelo P CobaZilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: coba@usc.edu.
University of Southern California · USSUNY Downstate Health Sciences University · US

Funding

Deciphering gene-environment interactions in pathological reactive aggressionR01MH104603 · NIMH · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Marco Bortolato, Regina A. Mangieri · 2014 to 2026
$6.0M
Validating Secretory Autophagy as a Therapeutic Strategy for Diverse Forms of ALS and FTDR01NS097850 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2016 to 2024
$5.5M
Regulation of postsynaptic protein interaction networks in complex brain disordersR01MH115005 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COBA, MARCELO PABLO · 2018 to 2022
$2.9M
Conversion of Fibroblasts to fxnal Spinal Motor Neurons Using Defined FactorR00NS077435 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2013 to 2015
$737k
Regulation of PSD phosphorylation and protein interactions networks by LTPR21MH113949 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COBA, MARCELO PABLO · 2017 to 2018
$437k
Conversion of fibroblasts to functional spinal motor neurons using defined factorK99NS077435 · NINDS · HARVARD UNIVERSITY · PI ICHIDA, JUSTIN KAWIKA · 2011 to 2012
$177k
NIMH NIH HHS R01 MH104603NIMH NIH HHS R01 MH115005NIMH NIH HHS R21 MH113949NINDS NIH HHS K99 NS077435NINDS NIH HHS R00 NS077435NINDS NIH HHS R01 NS097850
6 · The paper itself

Abstract

backgroundDisrupted in schizophrenia 1 (DISC1) has been implicated in a number of psychiatric diseases along with neurodevelopmental phenotypes such as the proliferation and differentiation of neural progenitor cells. While there has been significant effort directed toward understanding the function of DISC1 through the determination of its protein-protein interactions within an in vitro setting, endogenous interactions involving DISC1 within a cell type-specific setting relevant to neural development remain unclear.

methodsUsing CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genome engineering technology, we inserted an endogenous 3X-FLAG tag at the C-terminus of the canonical DISC1 gene in human induced pluripotent stem cells (iPSCs). We further differentiated these cells and used affinity purification to determine protein-protein interactions involving DISC1 in iPSC-derived neural progenitor cells and astrocytes.

resultsWe were able to determine 151 novel cell type-specific proteins present in DISC1 endogenous interactomes. The DISC1 interactomes can be clustered into several subcomplexes that suggest novel DISC1 cell-specific functions. In addition, the DISC1 interactome in iPSC-derived neural progenitor cells associates in a connected network containing proteins found to harbor de novo mutations in patients affected by schizophrenia and contains a subset of novel interactions that are known to harbor syndromic mutations in neurodevelopmental disorders.

conclusionsEndogenous DISC1 interactomes within iPSC-derived human neural progenitor cells and astrocytes are able to provide context to DISC1 function in a cell type-specific setting relevant to neural development and enables the integration of psychiatric disease risk factors within a set of defined molecular functions.

Indexed as

Cell DifferentiationAstrocytesCells, CulturedClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9HumansInduced Pluripotent Stem CellsMutationNerve Tissue ProteinsNeural Stem CellsNeurodevelopmental DisordersProtein Interaction MapsSchizophreniaCRISPR-Associated Protein 9DISC1 protein, humanNerve Tissue ProteinsCRISPRDISC1Neural developmentNeurodevelopmental disordersProteomicsSchizophrenia

Identifiers

PMID29961565
PMCPMC6251761
OpenAlexW2804789878

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.