Evidence map›Paper›PMID 36796362›Full record

ArticleCell stem cell2023

Natural variation in gene expression and viral susceptibility revealed by neural progenitor cell villages.

Michael F Wells, James Nemesh, Sulagna Ghosh, Jana M Mitchell, Max R Salick, Curtis J Mello, Daniel Meyer, Olli Pietilainen, Federica Piccioni, Ellen J Guss and 17 more

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

Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
16.6field-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

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 3 institutions in 1 country.

Michael F WellsStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Human Genetics, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
James NemeshStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Sulagna GhoshStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jana M MitchellStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Insitro, South San Francisco, CA 94080, USA.
Max R SalickInsitro, South San Francisco, CA 94080, USA.
Curtis J MelloStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Daniel MeyerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Olli PietilainenStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Federica PiccioniGenetic Perturbation Platform, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Ellen J GussDepartment of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Kavya RaghunathanStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Matthew TegtmeyerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Derek HawesStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Anna NeumannStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Kathleen A WorringerDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Daniel HoDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Sravya KommineniDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Karrie ChanDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Brant K PetersonDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Joseph J RaymondDepartment of Neuroscience, Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
John T GoldDepartment of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Biology, Davidson College, Davidson, NC 28035, USA.
Marco T SiekmannDepartment of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Emanuela ZuccaroDepartment of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Ralda NehmeStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Ajamete KaykasInsitro, South San Francisco, CA 94080, USA.
Kevin EgganStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: kevin.eggan@bmrn.com.
Steven A McCarrollStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: smccarro@broadinstitute.org.
Broad Institute · USNovartis (United States) · USHarvard University · US

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
Unraveling the Genetic Programs Engaged in ASD Neurons Through Coupled Transcriptomic and Phenotypic ReadoutsR01MH128366 · NIMH · BROAD INSTITUTE, INC. · PI Samouil Farhi, Ralda Nehme · 2022 to 2026
$3.7M
The role of autism susceptibility genes in the 16p11.2 locus on the development and function of human stem cell-derived neural cellsR00MH119327 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WELLS, MICHAEL FREDERICK · 2022 to 2024
$747k
The role of autism susceptibility genes in the 16p11.2 locus on the development and function of human stem cell-derived neural cellsK99MH119327 · NIMH · BROAD INSTITUTE, INC. · PI WELLS, MICHAEL FREDERICK · 2019 to 2021
$227k
NIMH NIH HHS K99 MH119327NIMH NIH HHS R00 MH119327NIMH NIH HHS R01 MH128366NIMH NIH HHS U01 MH105669NIMH NIH HHS U01 MH115727
6 · The paper itself

Abstract

Human genome variation contributes to diversity in neurodevelopmental outcomes and vulnerabilities; recognizing the underlying molecular and cellular mechanisms will require scalable approaches. Here, we describe a "cell village" experimental platform we used to analyze genetic, molecular, and phenotypic heterogeneity across neural progenitor cells from 44 human donors cultured in a shared in vitro environment using algorithms (Dropulation and Census-seq) to assign cells and phenotypes to individual donors. Through rapid induction of human stem cell-derived neural progenitor cells, measurements of natural genetic variation, and CRISPR-Cas9 genetic perturbations, we identified a common variant that regulates antiviral IFITM3 expression and explains most inter-individual variation in susceptibility to the Zika virus. We also detected expression QTLs corresponding to GWAS loci for brain traits and discovered novel disease-relevant regulators of progenitor proliferation and differentiation such as CACHD1. This approach provides scalable ways to elucidate the effects of genes and genetic variation on cellular phenotypes.

Indexed as

Neural Stem CellsZika VirusZika Virus InfectionBrainCell DifferentiationGene ExpressionHumansMembrane ProteinsRNA-Binding ProteinsIFITM3 protein, humanMembrane ProteinsRNA-Binding ProteinsCACHD1cell villagesCRISPR-Cas9 screenneural progenitor cellsneurodevelopmental disordersNeurogenin-2proliferationZika virus

Identifiers

PMID36796362
PMCPMC10581885
OpenAlexW4320914072

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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.