Evidence map›Paper›PMID 26299970›Full record

ArticleCell reports2015

Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate.

Priya Srikanth, Karam Han, Dana G Callahan, Eugenia Makovkina, Christina R Muratore, Matthew A Lalli, Honglin Zhou, Justin D Boyd, Kenneth S Kosik, Dennis J Selkoe and 1 more

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

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Pooled it
  2. Article
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  7. Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025
    Review
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  19. Brain organoids: Establishment and application.Frontiers in cell and developmental biology · 2022
    Review
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Priya SrikanthAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Harvard MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
Karam HanAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Dana G CallahanAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Eugenia MakovkinaAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Christina R MuratoreAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Matthew A LalliNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Honglin ZhouNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Justin D BoydAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Kenneth S KosikNeuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, Biomolecular Science and Engineering Program, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Dennis J SelkoeAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: tyoung@rics.bwh.harvard.edu.
Harvard University · USUniversity of California, Santa Barbara · USBrigham and Women's Hospital · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
AGING IN THE BRAIN--ROLE OF THE FIBROUS PROTEINSR01AG006173 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SELKOE, DENNIS J · 1985 to 2016
$2.5M
Genes and developmental signaling pathways in neuropsychiatric disordersR01MH101148 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2014 to 2018
$2.5M
Functions of DISC1 and APP in Cortical Development and Neuropsychiatric DisordersR00MH085004 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2011 to 2013
$717k
Identifying critical functions of DISC1 disrupted in major mental illnessF30MH103890 · NIMH · HARVARD MEDICAL SCHOOL · PI SRIKANTH, PRIYA · 2014 to 2015
$83k
NIA NIH HHS 2R01AG006173-26NIA NIH HHS R01 AG006173NIA NIH HHS T32 AG000222NIA NIH HHS T32AG000222NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753NIMH NIH HHS 1F30MH103890-01A1NIMH NIH HHS F30 MH103890NIMH NIH HHS R00 MH085004NIMH NIH HHS R00MH085004NIMH NIH HHS R01 MH101148NIMH NIH HHS R01MH101148
6 · The paper itself

Abstract

Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1) as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11) translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

Indexed as

NeurogenesisWnt Signaling PathwayCells, CulturedForkhead Transcription FactorsGenome, HumanHumansInduced Pluripotent Stem CellsNerve Tissue ProteinsNeural Stem CellsNonsense Mediated mRNA DecayProtein IsoformsT-Box Domain ProteinsTranslocation, GeneticDISC1 protein, humanEOMES protein, humanForkhead Transcription FactorsFOXG1 protein, humanNerve Tissue ProteinsProtein IsoformsT-Box Domain Proteins

Identifiers

PMID26299970
PMCPMC4558300
OpenAlexW1635914561

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.