Cited by 295Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersPluripotent Stem Cells Research

Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons

Open access
Schafer, Simon T., Paquola, Apua C. M., Stern, Shani, Gosselin, David, Ku, Manching, Pena, Monique, Kuret, Thomas J. M., Liyanage, Marvin +6 more·2019·Nature Neuroscience

Abstract

Autism spectrum disorder (ASD) is thought to emerge during early cortical development. However, the exact developmental stages and associated molecular networks that prime disease propensity are elusive. To profile early neurodevelopmental alterations in ASD with macrocephaly, we monitored subject-derived induced pluripotent stem cells (iPSCs) throughout the recapitulation of cortical development. Our analysis revealed ASD-associated changes in the maturational sequence of early neuron development, involving temporal dysregulation of specific gene networks and morphological growth acceleration. The observed changes tracked back to a pathologically primed stage in neural stem cells (NSCs), reflected by altered chromatin accessibility. Concerted over-representation of network factors in control NSCs was sufficient to trigger ASD-like features, and circumventing the NSC stage by direct conversion of ASD iPSCs into induced neurons abolished ASD-associated phenotypes. Our findings identify heterochronic dynamics of a gene network that, while established earlier in development, contributes to subsequent neurodevelopmental aberrations in ASD.

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/s41593-018-0295-x

Cites

71 of 71 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?

  • Compared with bulk adult brain region signatures from the Allen BrainSpan dataset, both iNs and iPSC-iNs are most similar to prefrontal and frontal adult human cortex samples and less similar to other regions.

    “Consistently, compared with gene expression signatures from bulk adult brain regions from the Allen BrainSpan dataset, both iNs and iPSC-iNs were most similar to prefrontal and frontal adult human cortex samples and less to other regions (Figure 7E; Mertens et al., 2015a; Schafer et al., 2019).”

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

Cited by

Sorted by citations

Authors
Schafer, S. T., Paquola, A. C. M., Stern, S., Gosselin, D., Ku, M., Pena, M., Kuret, T. J. M., Liyanage, M., Mansour, A. A., Jaeger, B. N., Marchetto, M. C., Glass, C. K., Mertens, J., & Gage, F. H.
Affiliations
  • Salk Institute for Biological Studies (US)
  • Centre hospitalier universitaire de Québec (CA)
  • University of California San Diego (US)
Corresponding author
Gage, Fred H.
Venue
Nature Neuroscience
Published
2019-01-07
Volume
22
Issue
2
Pages
243-255
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2906812748
Cited by
288
References
71
Citations by year
2026: 18 · 2025: 34 · 2024: 25 · 2023: 35 · 2022: 40 · 2021: 44 · 2020: 63 · 2019: 28
FWCI
25.58
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG056306)
  • National Institute of Mental Health (R01MH090258, R03MH115426, R01MH095741)
  • National Cancer Institute (P30CA014195)
  • National Institute of Neurological Disorders and Stroke (R01NS096170)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
autism spectrum disorder, heterochrony, cortical development, neural stem cells, induced neurons, induced pluripotent stem cells, chromatin accessibility, macrocephaly, iPSC-derived neurons
MeSH terms
Autism Spectrum Disorder, Humans, Nerve Net, Neurons, Gene Regulatory Networks, Inhibitory Postsynaptic Potentials, Induced Pluripotent Stem Cells, Neural Stem Cells

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