Related Experiment Video
Updated: Sep 9, 2025
10:25
Generation of Standardized and Reproducible Forebrain-type Cerebral Organoids from Human Induced Pluripotent Stem Cells
Published on: January 23, 2018
21.6K
A mouse organoid platform for modeling cerebral cortex development and cis-regulatory evolution in vitro
Daniel Medina-Cano1, Mohammed T Islam1, Veronika Petrova2
1Developmental Biology Program, Center for Stem Cell Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Developmental Cell
|August 28, 2025
Summary
Researchers developed a new method to grow cerebral cortex organoids from mouse stem cells. This technique reveals gene regulatory variations that explain differences in brain structure and function across mammal evolution.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Gene regulatory networks guide mammalian cortical development, resulting in diverse brain structures and functions.
- The molecular mechanisms driving these evolutionary changes in the cerebral cortex remain largely uncharacterized.
Purpose of the Study:
- To develop a reproducible protocol for generating cerebral cortex organoids from mouse epiblast stem cells (EpiSCs).
- To comprehensively map cis-acting transcriptional regulatory variation across developing cortical cell types using organoids from diverse mouse strains.
- To investigate the developmental mechanisms underlying evolutionary changes in cortical structure and function.
Main Methods:
- Generation of cerebral cortex organoids from F1 hybrid EpiSCs derived from crosses between laboratory mice and four wild-derived inbred strains.
- Application of single-cell RNA sequencing (scRNA-seq) to analyze gene expression and allelic imbalances in developing cortical cell types within organoids.
- Utilizing organoids from strains with approximately 1 million years of evolutionary divergence to capture regulatory variation.
Main Results:
- Successful recapitulation of embryonic cortical timing and cellular differentiation programs in generated organoids.
- Identification of hundreds of genes exhibiting dynamic allelic imbalances during cortical development.
- The study provides the first insights into developmental mechanisms driving cortical evolution through cis-acting regulatory variation.
Conclusions:
- The developed cerebral cortex organoid protocol is a reproducible and powerful platform for studying gene regulation in the developing brain.
- This research illuminates the genetic basis of evolutionary adaptations in mammalian brain structure and function.
- The findings offer a valuable resource for future investigations into neurodevelopmental processes and evolutionary genomics.
