Evidence map›Paper›PMID 36596304›Full record

ArticleCell reports2023

Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues.

Francesco Limone, Irune Guerra San Juan, Jana M Mitchell, Janell L M Smith, Kavya Raghunathan, Daniel Meyer, Sulagna Dia Ghosh, Alexander Couto, Joseph R Klim, Brian J Joseph and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 45 citations in OpenAlex.

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  9. Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026
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  19. Generation ofbioRxiv : the preprint server for biology · 2025
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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

19 authors at 3 institutions in 3 countries.

Francesco LimoneDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Leiden University Medical Center, LUMC, 2333 ZA Leiden, the Netherlands. Electronic address: francesco_limone@fas.harvard.edu.
Irune Guerra San JuanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, the Netherlands; Human Genetics, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Jana M MitchellDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Janell L M SmithDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Kavya RaghunathanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel MeyerStanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Sulagna Dia GhoshDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Alexander CoutoDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Joseph R KlimDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Brian J JosephDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Departments of Pathology and Cell Biology, Columbia University Irving Medical Centre, New York, NY 10032, USA.
John GoldDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Curtis J MelloStanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
James NemeshStanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Brittany M SmithDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Matthijs VerhageDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, the Netherlands; Human Genetics, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Steven A McCarrollStanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Olli PietiläinenDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Neuroscience Center, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
Ralda NehmeDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kevin EgganDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: kevin.eggan@bmrn.com.
Broad Institute · USHarvard University · USCognitive Research (United States) · 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
NIMH NIH HHS U01 MH115727
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) are a powerful tool for disease modeling of hard-to-access tissues (such as the brain). Current protocols either direct neuronal differentiation with small molecules or use transcription-factor-mediated programming. In this study, we couple overexpression of transcription factor Neurogenin2 (Ngn2) with small molecule patterning to differentiate hPSCs into lower induced motor neurons (liMoNes/liMNs). This approach induces canonical MN markers including MN-specific Hb9/MNX1 in more than 95% of cells. liMNs resemble bona fide hPSC-derived MN, exhibit spontaneous electrical activity, express synaptic markers, and can contact muscle cells in vitro. Pooled, multiplexed single-cell RNA sequencing on 50 hPSC lines reveals reproducible populations of distinct subtypes of cervical and brachial MNs that resemble their in vivo, embryonic counterparts. Combining small molecule patterning with Ngn2 overexpression facilitates high-yield, reproducible production of disease-relevant MN subtypes, which is fundamental in propelling our knowledge of MN biology and its disruption in disease.

Indexed as

CuesInduced Pluripotent Stem CellsCell DifferentiationGene Expression RegulationHomeodomain ProteinsHumansMotor NeuronsTranscription FactorsHomeodomain ProteinsMNX1 protein, humanTranscription FactorsCP: NeuroscienceCP: Stem cell researchdifferentiation protocolDropulationhuman stem cellsmotor neuronmultiplexed pooled sequencingneuronal differentiationNGN2patterning moleculessingle cell profilingspinal cord

Identifiers

PMID36596304
PMCPMC10117176
OpenAlexW4313406597

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.