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Chromatin accessibility dynamics in a model of human forebrain development
Open accessAbstract
Organoids recapitulate brain development: Gene expression changes and their control by accessible chromatin in the human brain during development is of great interest but limited accessibility. Trevino et al. avoided this problem by developing three-dimensional organoid models of human forebrain development and examining chromatin accessibility and gene expression at the single-cell level. From this analysis, they matched developmental profiles between the organoid and fetal samples, identified transcription factor binding profiles, and predicted how transcription factors are linked to cortical development. The researchers were able to correlate the expression of neurodevelopmental disease risk loci and genes with specific cell types during development. Science , this issue p. eaay1645
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“However, cellular heterogeneity poses significant challenges for unraveling the complexity in the gene regulatory architecture of the human brain, as it is comprised of heterogeneous cell populations, mostly different types of neurons and glia, each of which display distinct gene expression3,8–10 and chromatin accessibility profiles11–14.”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [14]
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Eichmüller, O. L., & Knoblich, J. A. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00723-9 · Cited by 319
Metadata
- Authors
- Trevino, A. E., Sinnott-Armstrong, N., Andersen, J., Yoon, S.-J., Huber, N., Pritchard, J. K., Chang, H. Y., Greenleaf, W. J., & Pașca, S. P.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Corresponding author
- Trevino, Alexandro E.
- Sinnott-Armstrong, Nasa
- Andersen, Jimena
- Greenleaf, William J.
- Pașca, Sergiu P.
- ORCID
- Venue
- Science
- Published
- 2020-01-24
- Volume
- 367
- Issue
- 6476
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7313757
- OpenAlex
- W3000751841
- Cited by
- 251
- References
- 78
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 39 · 2023: 36 · 2022: 56 · 2021: 42 · 2020: 22
- FWCI
- 12.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R01MH107800, U01MH115745)
- National Human Genome Research Institute (RM1HG007735, P50HG007735, UM1HG009442)
- National Institute of Allergy and Infectious Diseases (U19AI090023, U19AI057266)
- 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 › Epigenetics and DNA Methylation
- Keywords
- chromatin accessibility, forebrain development, cortical development, three-dimensional organoids, glial lineage, neuronal lineage, transcription factors, neuropsychiatric disorders, genetic risk, evolutionary conservation, gene regulatory dynamics
- MeSH terms
- Animals, Mental Disorders, Chromatin, Humans, Nervous System Diseases, Organoids, Prosencephalon, Gene Expression Regulation, Developmental, Cell Lineage, Pluripotent Stem Cells, Chromatin Assembly and Disassembly, Mice, Neurogenesis, Transcriptome
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