Evidence map›Paper›PMID 29791859›Full record

ArticleCell reports2018

Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission.

Ralda Nehme, Emanuela Zuccaro, Sulagna Dia Ghosh, Chenchen Li, John L Sherwood, Olli Pietilainen, Lindy E Barrett, Francesco Limone, Kathleen A Worringer, Sravya Kommineni and 11 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 1 pooled it
9.5field-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

192 citing papers in PubMed, 1 synthesis or guideline pooled it, 269 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  10. Article
  11. Molecular Acrobats: How CHD Remodelers Shape the Genetic Playground to License Cell Identity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  12. Article
  13. Excitatory Dysfunction and Phenotypic Rescue in a Human Neuronal Model ofbioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Astrocyte Enrichment of 3D Cortical Constructs Enhances Brain Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  19. Article
  20. Article

132 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

21 authors at 6 institutions in 3 countries.

Ralda NehmeStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Emanuela ZuccaroStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Sulagna Dia GhoshStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Chenchen LiStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
John L SherwoodStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Olli PietilainenStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Lindy E BarrettStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Francesco LimoneStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Kathleen A WorringerNovartis Institutes for Biomedical Research, Novartis, Cambridge, MA 02139, USA.
Sravya KommineniNovartis Institutes for Biomedical Research, Novartis, Cambridge, MA 02139, USA.
Ying ZangStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Davide CacchiarelliDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Alex MeissnerDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Rolf AdolfssonUmea University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry, 901 85 Umea, Sweden.
Stephen HaggartyCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Jon MadisonStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Matthias MullerNovartis Institutes for Biomedical Research, Novartis, 4056 Basel, Switzerland.
Paola ArlottaStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Zhanyan FuStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Guoping FengStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; McGovern Institute for Brain Research in the Department of Brain and Cognitive Sciences at MIT, Cambridge, MA 02139, USA.
Kevin EgganStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: eggan@mcb.harvard.edu.
Broad Institute · USHarvard University · USNovartis (United States) · USMassachusetts General Hospital · USNovartis (Switzerland) · CHUmeå University · SE

Funding

Genetic neuroscience: How human genes and alleles shape neuronal phenotypesU01MH115727 · NIMH · BROAD INSTITUTE, INC. · PI ARLOTTA, PAOLA, BABADI, MEHRTASH · 2017 to 2021
$20.8M
3/3-Identifying regulatory mutations that influence neuropsychiatric diseaseU01MH105669 · NIMH · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH · 2014 to 2018
$4.5M
NIMH NIH HHS U01 MH105669NIMH NIH HHS U01 MH115727
6 · The paper itself

Abstract

Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report that combining NGN2 programming with SMAD and WNT inhibition generates human patterned induced neurons (hpiNs). Single-cell analyses showed that hpiN cultures contained cells along a developmental continuum, ranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene and exhibited greater functionality, including NMDAR-mediated synaptic transmission. We conclude that utilizing single-cell and reporter gene approaches for selecting successfully programmed cells for study will greatly enhance the utility of hpiNs and other programmed neuronal populations in the modeling of nervous system disorders.

Indexed as

Body PatterningSynaptic TransmissionAdultBasic Helix-Loop-Helix ProteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell DifferentiationCells, CulturedFetusGene Expression RegulationHumansNerve Tissue ProteinsNeuronsPluripotent Stem CellsReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateBasic Helix-Loop-Helix ProteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2Nerve Tissue ProteinsNEUROG2 protein, humanReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateSmad ProteinsWnt ProteinsAMPARCAMK2Adual SMAD inhibitionexcitatory neuronshuman stem cellneuronal differentiationNGN2NMDARsingle cell profilingWnt inhibition

Identifiers

PMID29791859
PMCPMC6003669
OpenAlexW2803649084

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.