Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders

Elke Gabriel; Jay Gopalakrishnan

doi:10.3791/55372

Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders

JoVE Journal
Developmental Biology

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JoVE Journal Developmental Biology

Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders

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07:40 min

April 14, 2017

DOI: 10.3791/55372-v

Elke Gabriel¹, Jay Gopalakrishnan^1,2

¹Center for Molecular Medicine Cologne,University of Cologne, ²Institute for Biochemistry I,Medical School of University of Cologne

Overview

This article describes a method for generating iPSC-derived human brain organoids to model early neurodevelopmental disorders, including microcephaly. The technique aims to provide insights into the complexities of human brain development.

Key Study Components

Area of Science

Neuroscience
Developmental Biology
Stem Cell Research

Background

Modeling human brain development is complex due to neural epithelial tissue.
Understanding early neurodevelopmental events is crucial for addressing disorders.
Microcephaly is a significant condition that can be modeled in vitro.
iPSC-derived organoids offer a promising approach for research.

Purpose of Study

To model early human neurodevelopmental disorders.
To investigate the role of synthesomes and cilia in neurogenesis.
To provide a robust method for generating reproducible brain organoids.

Methods Used

Collection of neurospheres using a micropipette.
Placement of neurospheres on paraffin film in a dish.
Utilization of iPSC-derived cells for organoid generation.
Demonstration of the procedure by a post-doc researcher.

Main Results

The method allows for quick and reproducible results.
Insights into the mechanisms of neurogenesis were gained.
The model can effectively simulate conditions like microcephaly.
Potential applications in studying other neurodevelopmental disorders.

Conclusions

This protocol enhances the understanding of human brain development.
It provides a valuable tool for studying neurodevelopmental disorders.
The approach can lead to new insights into therapeutic strategies.

Frequently Asked Questions

What are brain organoids?

Brain organoids are 3D structures derived from stem cells that mimic the architecture and function of the human brain.

How are iPSC-derived brain organoids generated?

They are generated from induced pluripotent stem cells through a series of culture and differentiation steps.

What is the significance of modeling microcephaly?

Modeling microcephaly helps researchers understand the underlying mechanisms and potential treatments for this condition.

Who demonstrated the procedure in the study?

The procedure was demonstrated by Elke Gabriel, a post-doc from the Center for Molecular Medicine, Cologne.

What are synthesomes and their role in neurogenesis?

Synthesomes are cellular structures involved in the synthesis of proteins and play a crucial role in the development of neurons.

Can this method be used for other neurodevelopmental disorders?

Yes, the method can potentially be adapted to study various neurodevelopmental disorders beyond microcephaly.

Modeling human brain development has been hindered due to the unprecedented complexity of neural epithelial tissue. Here, a method for the robust generation of brain organoids to delineate early events of human brain development and to model microcephaly in vitro is described.

The overall goal of this protocol for generating iPSC-derived Human Brain Organoids is to model early human neurodevelopmental disorders. This method can help answer key questions in the human brain development field such as the role of synthesomes and cilia in novel neurogenesis and primary microcephaly. The main advantage of this technique is that it is a robust and quick model to obtain reproducible results from patient's iPSC-derived brain organites.

Demonstrating the procedure will be Elke Gabriel, a post-doc from my laboratory at the Center for Molecular Medicine, Cologne. To begin this procedure, collect the neurospheres with a 200 microliter micropipette using a two millimeter tip previously cut with sterile scissors. Next, place the neurospheres approximately five milliliters away from each other on a paraffin film in a 100 milliliter dish.

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