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Updated: Aug 9, 2025
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Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
Published on: March 2, 2018
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Massively parallel characterization of psychiatric disorder-associated and cell-type-specific regulatory elements in
Chengyu Deng1,2, Sean Whalen3, Marilyn Steyert4,5,6
1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco; San Francisco, CA, USA.
Biorxiv : the Preprint Server for Biology
|February 24, 2023
Summary
Researchers mapped gene regulatory elements in human brain development. They found 164 variants linked to psychiatric disorders that alter gene activity, creating a key resource for neurodevelopmental research.
Area of Science:
- Genetics and Genomics
- Neuroscience
- Developmental Biology
Background:
- Gene regulatory elements critically influence neuronal development and are implicated in neurological diseases.
- Understanding these elements is essential for deciphering the genetic basis of brain disorders.
Approach:
- Massively parallel reporter assays were employed in primary human cortical cells and cerebral organoids to test the cis-regulatory activity of over 100,000 DNA sequences.
- Sequences included cell-type specific regions and single-nucleotide variants associated with psychiatric disorders.
- Deep learning models were utilized to analyze sequence patterns and identify upstream regulators of enhancer activity.
Key Points:
- Identified 46,802 active enhancer sequences in developing human cortical cells.
- Discovered 164 psychiatric disorder-associated variants that significantly modulate enhancer activity.
- Demonstrated comparable enhancer activity in cerebral organoids and primary cells, validating organoids as a model for cortical development.
Conclusions:
- This study provides a comprehensive catalog of functional gene regulatory elements and disease-associated variants in human neuronal development.
- The findings offer insights into the sequence basis and regulatory mechanisms of enhancers.
- This resource is valuable for future research into the genetic underpinnings of neurodevelopmental and psychiatric disorders.
