Cited by 343Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Generation of pure GABAergic neurons by transcription factor programming

Open access
Yang, Nan, Chanda, Soham, Marro, Samuele, Ng, Yi-Han, Janas, Justyna A, Haag, Daniel, Ang, Cheen Euong, Tang, Yunshuo +10 more·2017·Nature Methods

Abstract

Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human PSCs. Here, we show that transient expression of the transcription factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic neurons from human PSCs with a high degree of synaptic maturation. These AD-induced neuronal (iN) cells represent largely nonoverlapping populations of GABAergic neurons that express various subtype-specific markers. We further used AD-iN cells to establish that human collybistin, the loss of gene function of which causes severe encephalopathy, is required for inhibitory synaptic function. The generation of defined populations of functionally mature human GABAergic neurons represents an important step toward enabling the study of diseases affecting inhibitory synaptic transmission.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nmeth.4291

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Induced expression of different transcription factors yields other neuron types, such as motor neurons and inhibitory neurons.

    “induced expression of different transcription factors yield other types of neurons, such as motor neurons (Hester et al., 2011; Shi et al., 2018) and inhibitory neurons (Yang et al., 2017).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 42 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Yang, N., Chanda, S., Marro, S., Ng, Y.-H., Janas, J. A., Haag, D., Ang, C. E., Tang, Y., Flores, Q., Mall, M., Wapinski, O., Li, M., Ahlenius, H., Rubenstein, J. L., Chang, H. Y., Buylla, A. A., Südhof, T. C., & Wernig, M.
Affiliations
  • Stanford Medicine (US)
  • University of California, San Francisco (US)
Corresponding author
Wernig, Marius
Venue
Nature Methods
Published
2017-05-15
Volume
14
Issue
6
Pages
621-628
ISSN
  • 1548-7091 (ISSN-L)
  • 1548-7105
OpenAlex
W2613062475
Cited by
341
References
42
Citations by year
2026: 21 · 2025: 42 · 2024: 28 · 2023: 41 · 2022: 44 · 2021: 51 · 2020: 48 · 2019: 34 · 2018: 23 · 2017: 5 · 2016: 1 · 2014: 1
FWCI
12.22
Type
journal article
Language
en
Open access
Locations
  • Nature Methods (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Institute of Mental Health (R01MH092931, U19MH104172, R01MH049428, R37MH049428)
  • National Human Genome Research Institute (P50HG007735)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD032116, R01HD032116)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
GABAergic neurons, ASCL1, Dlx2, human pluripotent stem cells, neuronal differentiation, synapse maturation, collybistin, synaptic inhibition, disease modeling
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Humans, Transcription Factors, Homeodomain Proteins, Pluripotent Stem Cells, Mice, Basic Helix-Loop-Helix Proteins, GABAergic Neurons, Cell Engineering

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review