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Updated: May 15, 2026
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Generation of Standardized and Reproducible Forebrain-type Cerebral Organoids from Human Induced Pluripotent Stem Cells
Published on: January 23, 2018
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Cell stress in cortical organoids impairs molecular subtype specification
Aparna Bhaduri1,2, Madeline G Andrews1,2, Walter Mancia Leon2
1Department of Neurology, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Nature
|January 31, 2020
Summary
Human brain organoids model the developing cerebral cortex but lack cellular diversity and proper cell maturation. Transplanting organoids into mice improves their accuracy for studying human brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Stem Cell Biology
Background:
- Cortical organoids are 3D cultures modeling human cerebral cortex development.
- The accuracy of these organoid models for recapitulating human brain development remains uncertain.
Purpose of the Study:
- To analyze and compare transcriptomes of individual primary human cortical cells and cortical organoids.
- To evaluate the fidelity of cortical organoids in modeling human brain development.
Main Methods:
- Single-cell transcriptome analysis of human cortical cells across developmental stages and areas.
- Transcriptome analysis of human cortical organoids.
- Comparison of gene expression profiles between in vivo cortical cells and organoids.
- Assessment of organoid defects after transplantation into mouse cortex.
Main Results:
- Human cortical development shows progenitor maturation, diverse cell subtypes, and areal neuron specification.
- Cortical organoids exhibit broad cell classes but lack distinct subtypes and proper progenitor maturation.
- Molecular signatures of cortical areas appear in organoid neurons but are not spatially organized.
- Organoids activate stress pathways, impairing cell-type specification, but transplantation mitigates these defects.
Conclusions:
- Cortical organoids partially model human brain development but have limitations in cellular diversity and maturation.
- Transplantation into mouse brains can improve organoid fidelity and alleviate stress-related defects.
- Developed datasets and tools offer a framework for assessing and enhancing cortical organoid accuracy.
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