Cited by 354Genomics and Chromatin DynamicsNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

The Dynamic Landscape of Open Chromatin during Human Cortical Neurogenesis

Open access
de la Torre-Ubieta, Luis, Stein, Jason L., Won, Hyejung, Opland, Carli K., Liang, Dan, Lu, Daning, Geschwind, Daniel H.·2018·Cell

Abstract

Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. We link distal regulatory elements (DREs) to their cognate gene(s) together with chromatin interaction data and show that target genes of human-gained enhancers (HGEs) regulate cortical neurogenesis and are enriched in outer radial glia, a cell type linked to human cortical evolution. We experimentally validate the regulatory effects of predicted enhancers for FGFR2 and EOMES. We observe that common genetic variants associated with educational attainment, risk for neuropsychiatric disease, and intracranial volume are enriched within regulatory elements involved in cortical neurogenesis, demonstrating the importance of this early developmental process for adult human cognitive function.

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 · 10.1016/j.cell.2017.12.014

Cites

92 of 92 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?

  • The major pathogenic mechanism of copy number variants is presumed to be dosage sensitivity of genes within the variant, although distal regulatory effects on genes outside the variant are also plausible.

    “the major pathogenic mechanism is presumed to be dosage-sensitivity of genes in the CNV although distal regulatory effects on genes outside of the CNV are also plausible (de la Torre-Ubieta et al., 2018)”

    From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as de la Torre-Ubieta et al., 2018

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

Research works printed but not linked: 1

  1. Rubenstein JLR Rakic P 2013 Comprehensive developmental neuroscience: patterning and cell type specification in the developing CNS and PNS First Amsterdam Elsevier/Academic Press

Cited by

Sorted by citations

Authors
de la Torre-Ubieta, L., Stein, J. L., Won, H., Opland, C. K., Liang, D., Lu, D., & Geschwind, D. H.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of California, Los Angeles (US)
Corresponding author
Geschwind, Daniel H.
Venue
Cell
Publisher
Elsevier BV
Published
2018-01
Volume
172
Issue
1-2
Pages
289-304.e18
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2782160930
Cited by
353
References
90
Citations by year
2026: 12 · 2025: 30 · 2024: 32 · 2023: 54 · 2022: 41 · 2021: 45 · 2020: 66 · 2019: 44 · 2018: 27
FWCI
16.19
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • NIH (5R37MH060233, 5R01MH100027, 3U01MH103339, 1R01MH110927, 1R01MH094714, R00MH102357, K99MH113823)
  • California Institute for Regenerative Medicine (CIRM)-BSCRC Training Grant (TG2-01169)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
open chromatin, cortical neurogenesis, non-coding regulatory elements, distal regulatory elements, chromatin accessibility, enhancer-gene interactions, outer radial glia, cortical development, FGFR2, Eomes, educational attainment, intracranial volume, human brain evolution
MeSH terms
Cell Line, Cells, Cultured, Cerebral Cortex, Chromatin, Enhancer Elements, Genetic, Female, Humans, Male, Neurons, Polymorphism, Genetic, Gene Expression Regulation, Developmental, T-Box Domain Proteins, Chromatin Assembly and Disassembly, Receptor, Fibroblast Growth Factor, Type 2, Neurogenesis

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