Angelman Syndrome iPSC and Brain Organoid Biorepository

Quick Overview

Dr. Yong-Hui Jiang presented a project at the 2020 FAST Science Summit to create a biorepository for Angelman Syndrome-induced pluripotent stem cells (iPSC) and brain organoids. The goal is to develop a novel treatment for Angelman Syndrome and similar disorders. iPSCs are generated from somatic cells and can be differentiated into various cell types, including neurons. Brain organoids are miniature human brain-like structures created from iPSCs. The project aims to generate multiple iPSC lines and brain organoids from different genotypes of Angelman Syndrome. The cells will be made available to researchers for further study and testing of potential treatments. The project is supported by FAST and is being conducted at Yale University.

Introduction

In this talk, we will discuss a project supported by FAST (Foundation for Angelman Syndrome Therapeutics) to create a biorepository for Angelman Syndrome-induced pluripotent stem cells (iPSC) and brain organoids. This project aims to develop a novel treatment for Angelman Syndrome and similar disorders.

Background

Angelman Syndrome is a genetic disorder caused by the deficiency of the UBE3A gene. Understanding the mechanism behind this deficiency is crucial for developing effective treatments. Animal models, such as mice, have been used to study the syndrome and test potential therapies. However, there are limitations to using animal models, as the differences between human and mouse brains can affect the translation of successful treatments.

iPSC and Brain Organoids

To overcome the limitations of animal models, researchers have developed techniques to generate induced pluripotent stem cells (iPSC) from somatic cells, such as skin cells or blood cells. iPSCs can be differentiated into various cell types, including neurons. Additionally, researchers have recently been able to create brain organoids, miniature structures resembling the human brain, using iPSCs.

Project Objective

The objective of this project is to create a biorepository for a panel of Angelman Syndrome iPSCs and brain organoids at Yale University. The plan is to generate multiple cell lines representing different genotypes of Angelman Syndrome, including deletions, mutations, uniparental disomy (UPD), and gain-of-function mutations. These cell lines will be made available to researchers and laboratories for further study and experimentation.

Project Phases

The project will be divided into two phases. In the first phase, which will last for one to two years, 20 iPSC lines will be generated from five different genotypes of Angelman Syndrome, along with five control iPSC lines. In the second phase, which will take place in the third or fourth year, brain organoids will be generated from the iPSC lines.

Call for Participation

The project is currently seeking Angelman Syndrome patients between the ages of five and 18 years old to participate. Both boys and girls are welcome, and a mix of patients with and without seizures is desired. The goal is to collect three patients from each genotype class (Class I to V) and five control individuals. Families with healthy siblings are encouraged to donate blood from the sibling for the project.

Research Team and Acknowledgments

The project is led by Dr. Yong-Hui Jiang at Yale University, with support from the Yale Stem Cell Center. Dr. Caihong Qiu is the iPSC Core Director, and Dr. Haifeng Hi is the Director for Stem Cell and Organoid Research. The research team is dedicated to the success of the project and aims to create all the cell lines needed for research and investigation worldwide.

The project would not be possible without the support of FAST, Allyson, the FAST board members, and the participating families. The researchers express their gratitude to everyone involved in the project and look forward to meeting them in person.

For more information or to participate in the project, please contact Dr. Yong-Hui Jiang or FAST for further details.