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Related Experiment Video

Updated: May 8, 2026

Ex utero Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development

Ex utero Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development

Published on: April 3, 2013

Massively parallel characterization of regulatory elements in the developing human cortex.

Chengyu Deng^1,2, Sean Whalen³, Marilyn Steyert^4,5,6,7,8,9

¹Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Science (New York, N.Y.)

|May 23, 2024

Summary

This summary is machine-generated.

This study maps gene regulatory elements in the human brain, identifying thousands of active enhancers and variants impacting neuronal development and disease. Cerebral organoids effectively model the developing cortex for this research.

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Published on: April 3, 2013

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Published on: March 25, 2022

Area of Science:

Genetics
Neuroscience
Developmental Biology

Background:

Nucleotide changes in gene regulatory elements significantly influence neuronal development and associated diseases.
Understanding these elements is crucial for deciphering brain function and pathology.

Purpose of the Study:

To comprehensively map and characterize cis-regulatory elements and their variants in the developing human brain.
To validate the use of cerebral organoids as a model for studying human cortical development.

Main Methods:

Massively parallel reporter assays were performed on primary human cortical cells and cerebral organoids.
Over 100,000 open chromatin regions were analyzed, including cell type-specific and disease-associated sequences.
Deep learning models were employed to decode sequence determinants and regulatory factors of enhancer activity.

Main Results:

Identified 46,802 active enhancer sequences in primary cells.
Discovered 164 variants that significantly alter enhancer activity.
Demonstrated comparable regulatory element activity in cerebral organoids and primary cortical cells.

Conclusions:

Cerebral organoids serve as a valid model for studying the developing human cortex.
This work provides a comprehensive catalog of functional gene regulatory elements and variants critical for human neuronal development.
The findings offer insights into the genetic basis of brain development and neurological disorders.