Evidence map›Paper›PMID 32989314›Full record

ArticleNature medicine2020

Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.

Themasap A Khan, Omer Revah, Aaron Gordon, Se-Jin Yoon, Anna K Krawisz, Carleton Goold, Yishan Sun, Chul Hoon Kim, Yuan Tian, Min-Yin Li and 17 more

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

Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 4 pooled it
9.4field-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

115 citing papers in PubMed, 4 syntheses or guidelines pooled it, 200 citations in OpenAlex.

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55 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

27 authors at 9 institutions in 3 countries.

Themasap A Khan *Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3626-1475
Omer Revah *Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4002-5689
Aaron Gordon *Program in Neurogenetics, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-7372-7185
Se-Jin YoonDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8412-5991
Anna K KrawiszDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Carleton GooldDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Yishan SunDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Chul Hoon KimDepartment of Neurobiology, Stanford University, Stanford, CA, USA.
Yuan TianProgram in Neurogenetics, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
Min-Yin LiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8102-632X
Julia M SchaepeDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Kazuya IkedaDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3671-5940
Neal D AminDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Noriaki SakaiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Masayuki YazawaDepartment of Neurobiology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5730-6583
Leila KushanDepartment of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
Seiji NishinoDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Matthew H PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3850-4648
Judith L RapoportNational Institute of Mental Health, Child Psychiatry Branch, Bethesda, MD, USA.
Jonathan A BernsteinDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5369-346X
Ruth O'HaraDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Carrie E BeardenDepartment of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8516-923X
Joachim F HallmayerDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
John R HuguenardDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Daniel H GeschwindProgram in Neurogenetics, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
Ricardo E DolmetschNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Sergiu P PaşcaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. spasca@stanford.edu.ORCID http://orcid.org/0000-0002-3216-3248
Stanford University · USUniversity of California, Los Angeles · USBeth Israel Deaconess Medical Center · USCalifornia Institute for Regenerative Medicine · USColumbia University · USNational Institute of Mental Health · USNeurosciences Institute · USNovartis (United States) · USYonsei University · KR

Funding

Neurodevelopment and Psychosis in the 22q11.2 Deletion SyndromeR01MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E · 2010 to 2020
$6.2M
Gaining insight into psychiatric disease by engineering piece by piece the human brain in vitro.R01MH107800 · NIMH · STANFORD UNIVERSITY · PI PASCA, SERGIU · 2015 to 2024
$5.6M
Inhibitory Controls of Thalamic NeuronsR01NS034774 · NINDS · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 1996 to 2021
$5.5M
1/2 Cross modal integration of molecular and physiological networks in ASDU01MH115746 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H, MEHTA, MAYANK R · 2017 to 2021
$5.3M
Identification and Characterization of Asymmetrically-Expressed GenesR37MH060233 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2006 to 2014
$5.3M
Integrative Molecular and Phenotype Analysis of 22q11.2 Deletion SyndromeR01MH100900 · NIMH · STANFORD UNIVERSITY · PI HALLMAYER, JOACHIM F · 2013 to 2017
$4.8M
Cross modal integration of molecular and physiological networks in ASD (2/2)U01MH115745 · NIMH · STANFORD UNIVERSITY · PI PASCA, SERGIU · 2017 to 2021
$4.0M
Neurodevelopment and Psychosis in the 22q11.2 Copy Number VariantsR37MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARRIE E BEARDEN · 2023 to 2026
$2.9M
Epigenetic and Transcriptional Dysregulation in Autism Spectrum DisorderR01MH094714 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2011 to 2015
$2.8M
Chronic Axon Hypofunction in Maternal Immune Activation Models of Neurodevelopmental DisordersR01MH121075 · NIMH · STANFORD UNIVERSITY · PI HUGUENARD, JOHN R · 2020 to 2023
$1.9M
Howard Hughes Medical InstituteNIMH NIH HHS R01 MH085953NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH100900NIMH NIH HHS R01 MH107800NIMH NIH HHS R01 MH121075NIMH NIH HHS R37 MH060233NIMH NIH HHS R37 MH085953NIMH NIH HHS U01 MH115745NIMH NIH HHS U01 MH115746NINDS NIH HHS R01 NS034774
6 · The paper itself

Abstract

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease.

Indexed as

AdultCalcium SignalingCell DifferentiationCerebral CortexDiGeorge SyndromeFemaleHumansInduced Pluripotent Stem CellsMaleNeuronsOrganoidsYoung Adult

Identifiers

PMID32989314
PMCPMC8525897
OpenAlexW3091490674

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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.