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

Elke Gabriel; Jay Gopalakrishnan

doi:10.3791/55372

JoVE Journal
Developmental Biology

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JoVE Journal Developmental Biology

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

初期の神経発達障害をモデル化するためのiPSC由来のヒト脳オルガノイドの生成

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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

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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.

神経上皮組織の前例のない複雑さのために、人間の脳の発達をモデル化することが妨げられてきました。ここでは、ヒトの脳発生の初期のイベントを明らかにし、in vitroで小頭症をモデル化するための脳オルガノイドの堅牢な生成方法について説明します。

iPS細胞由来ヒト脳オルガノイドを作製するためのこのプロトコルの全体的な目標は、初期のヒト神経発達障害をモデル化することです。この方法は、新規の神経新生や原発性小頭症における合成体や繊毛の役割など、ヒトの脳発生分野における重要な疑問に答えるのに役立ちます。この技術の主な利点は、患者のiPS細胞由来の脳器官から再現性のある結果を得るための堅牢で迅速なモデルであることです。

この手順を実演するのは、ケルンの分子医学センターの私の研究室のポスドクであるElke Gabrielです。この手順を開始するには、滅菌ハサミで以前に切断した2ミリメートルの先端を使用して、200マイクロリットルのマイクロピペットでニューロスフェアを収集します。次に、ニューロスフィアを互いに約5ミリリットル離して、100ミリリットルの皿のパラフィンフィルムに置きます。

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