Related Experiment Video
Updated: May 2, 2026
07:40
Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders
Published on: April 14, 2017
20.7K
Single-cell brain organoid screening identifies developmental defects in autism.
Chong Li1, Jonas Simon Fleck2, Catarina Martins-Costa3
1Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna, Austria. chong.li@imba.oeaw.ac.at.
Nature
|September 13, 2023
Summary
We developed a CRISPR-based system to screen genes linked to autism spectrum disorder in human brain organoids. This method identified vulnerable cell types and gene networks affected by these mutations.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Human brain development has unique processes that can lead to neurodevelopmental disorders.
- Cerebral organoids offer a model to study these disorders in a human context.
Purpose of the Study:
- To develop a high-throughput screening system for identifying genes contributing to neurodevelopmental disorders.
- To investigate the effects of perturbing autism spectrum disorder-associated genes on human brain organoid development.
Main Methods:
- Developed the CRISPR-human organoids-single-cell RNA sequencing (CHOOSE) system for pooled loss-of-function screening.
- Utilized inducible CRISPR-Cas9 for genetic disruption and single-cell transcriptomics in mosaic organoids.
- Constructed a developmental gene regulatory network from single-cell transcriptomes and chromatin data.
Main Results:
- Perturbation of 36 high-risk autism spectrum disorder genes revealed impacts on cell fate determination.
- Dorsal intermediate progenitors, ventral progenitors, and upper-layer excitatory neurons were identified as vulnerable cell types.
- Disruption of the ARID1B subunit of the BAF chromatin remodeling complex affected progenitor cell fate transitions.
Conclusions:
- The CHOOSE system enables efficient screening of disease susceptibility genes in organoid models.
- This study identified critical cell types and gene regulatory networks involved in neurodevelopmental disorders.
- Findings provide a foundation for high-throughput phenotypic characterization of genes in organoid systems.
Related Concept Videos
01:30Neurulation
40.2K
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
40.2K
01:29Alzheimer Disease l: Introduction
21
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
21
01:22Dementia l: Introduction
35
Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
35