Evidence map›Paper›PMID 29727680›Full record

ArticleCell stem cell2018

Efficient Generation of CA3 Neurons from Human Pluripotent Stem Cells Enables Modeling of Hippocampal Connectivity In Vitro.

Anindita Sarkar, Arianna Mei, Apua C M Paquola, Shani Stern, Cedric Bardy, Jason R Klug, Stacy Kim, Neda Neshat, Hyung Joon Kim, Manching Ku and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 2 pooled it
6.9field-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

81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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  6. Reprogramming of neuronal genome function and phenotype by astrocytes.bioRxiv : the preprint server for biology · 2026
    Article
  7. Review
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  12. Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 1 institution in 2 countries.

Anindita SarkarLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: anindsarkar@gmail.com.
Arianna MeiLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Apua C M PaquolaLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; The Lieber Institute for Brain Development, Johns Hopkins School of Medicine, 855 N Wolfe Street, Baltimore, MD 21205, USA.
Shani SternLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cedric BardyLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Laboratory for Human Neurophysiology and Genetics, SAHMRI and College of Medicine and Public Health, Flinders University, Adelaide SA 5000, Australia.
Jason R KlugMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Stacy KimLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neda NeshatLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hyung Joon KimLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Psychiatry, Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198-5965, USA.
Manching KuNext Generation Sequencing Core, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Maxim N ShokhirevRazavi Newman Integrative Genomics and Bioinformatics Core Facility, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
David H AdamowiczLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Neurosciences, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Maria C MarchettoLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Roberto JappelliLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jennifer A ErwinLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; The Lieber Institute for Brain Development, Johns Hopkins School of Medicine, 855 N Wolfe Street, Baltimore, MD 21205, USA.
Krishnan PadmanabhanLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 603, Rochester, NY 14642, USA.
Matthew ShtrahmanLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Neurosciences, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Xin JinMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Fred H GageLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: gage@salk.edu.
Salk Institute for Biological Studies · US

Funding

Role of CACNA1C - a shared risk gene in neuropsychiatric disordersU19MH106434 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI SONG, HONGJUN · 2016 to 2020
$13.8M
3/3-Schizophrenia Genetics and Brain Somatic MosaicismU01MH106882 · NIMH · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2015 to 2019
$5.3M
Salk Institute for Biological Studies NINDS Center Core GrantP30NS072031 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI O'LEARY, DENNIS D · 2011 to 2015
$4.2M
in vivo imaging of transplanted human induced-Pluripotent Stem Cell (iPSC) derived neurons to model neurological and psychiatric disordersR01MH113924 · NIMH · UNIVERSITY OF ROCHESTER · PI PADMANABHAN, KRISHNAN · 2017 to 2021
$2.3M
The Role of Adult-born Dentate Granule Cells in EpileptogenesisK08NS093130 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHTRAHMAN, MATTHEW · 2016 to 2020
$1.0M
ENGRAFTING HUMAN NEURONS INTO ANIMAL MODELS TO STUDY SCHIZOPHRENIAR00MH101634 · NIMH · UNIVERSITY OF ROCHESTER · PI PADMANABHAN, KRISHNAN · 2016 to 2018
$731k
Engrafting human neurons into animal models to study schizophreniaK99MH101634 · NIMH · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI PADMANABHAN, KRISHNAN · 2013 to 2014
$175k
NIMH NIH HHS K99 MH101634NIMH NIH HHS R00 MH101634NIMH NIH HHS R01 MH113924NIMH NIH HHS U01 MH106882NIMH NIH HHS U19 MH106434NINDS NIH HHS K08 NS093130NINDS NIH HHS P30 NS072031
6 · The paper itself

Abstract

Despite widespread interest in using human induced pluripotent stem cells (hiPSCs) in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a comprehensive and efficient differentiation paradigm for hiPSCs that generate multiple CA3 pyramidal neuron subtypes as detected by single-cell RNA sequencing (RNA-seq). This differentiation paradigm exhibits characteristics of neuronal network maturation, and rabies virus tracing revealed synaptic connections between stem cell-derived dentate gyrus (DG) and CA3 neurons in vitro recapitulating the neuronal connectivity within the hippocampus. Because hippocampal dysfunction has been implicated in schizophrenia, we applied DG and CA3 differentiation paradigms to schizophrenia-patient-derived hiPSCs. We detected reduced activity in DG-CA3 co-culture and deficits in spontaneous and evoked activity in CA3 neurons from schizophrenia-patient-derived hiPSCs. Our approach offers critical insights into the network activity aspects of schizophrenia and may serve as a promising tool for modeling diseases with hippocampal vulnerability. VIDEO ABSTRACT.

Indexed as

AdultAnimalsCell DifferentiationDentate GyrusFemaleHippocampusHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLMice, Inbred NODMice, SCIDMiddle AgedNeuronsSchizophreniaCA3DGdisease-in-a-dishhippocampusneuronal diversitypyramidal neuronsrabies tracingschizophreniasingle cell sequencingsynaptic connectivity

Identifiers

PMID29727680
PMCPMC6345574
OpenAlexW2800420110

What OpenQuestion holds

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Registered trials

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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.