Benefits and Challenges of Human Cerebral Organoids for Angelman Syndrome Research

Quick Overview

In this presentation, Albert Keung discusses the use of human cerebroorganoids as a model system for studying Angelman Syndrome. He explains that human cerebroorganoids are microtissues composed of human cells that reflect the cellular and molecular properties of the human brain. These organoids can capture the diversity of cell types in the human brain and can be generated from patient-derived or genetically engineered cells to reflect specific genotypes associated with Angelman Syndrome. Keung demonstrates how these organoids can be used to study the functional impacts of Angelman deletions and test potential therapeutics. He also highlights the limitations of organoids, such as their inability to capture behavior. Keung concludes by expressing his hope to develop a genome engineering editing platform to generate cell lines that reflect specific genotypes, and he thanks FAST for their support in this research.

Introduction

In this talk, Albert Keung, a faculty member in the Chemical and Biomolecular Engineering Department at North Carolina State University, discusses the benefits and challenges of using human cerebral organoids for Angelman Syndrome research. He highlights the importance of diversity in cell types and genetic origins in understanding the disease and developing therapeutics. Keung also introduces the concept of human cerebroorganoids and their potential to provide a more accurate model for studying Angelman Syndrome.

The Importance of Diversity in Cell Types and Genetic Origins

Keung emphasizes the significance of understanding the diversity of cell types and genetic origins in the human brain when studying Angelman Syndrome. He explains that different types of neurons play various roles in the brain and understanding which cell types are affected in Angelman Syndrome is crucial for targeted therapeutic development. Additionally, the genetic diversity among individuals with Angelman Syndrome poses challenges in determining the specific impacts of different genotypes on neuronal function and development.

Introducing Human Cerebroorganoids

Keung introduces human cerebroorganoids as a relatively new model system that can address the challenges of studying Angelman Syndrome. These organoids are microtissues composed of human cells that reflect the cellular and molecular properties of the human brain. They contain diverse cell types and can mimic the layers found in the outer region of a real human brain. Keung explains that organoids provide an efficient way to study the complexity of the human brain and capture the maturation and development of different cell types over time.

Capturing Diversity in Cell Types and Genotypes

Keung discusses how human cerebroorganoids can capture the diversity of cell types and genotypes associated with Angelman Syndrome. He explains that organoids can be generated from pluripotent stem cells derived from patients, reflecting their specific genotypes. By studying these organoids, researchers can understand the functional impacts of different genotypes and test potential therapeutics. Keung also mentions the challenges of genome engineering and the goal of developing a genome editing platform to facilitate the creation of organoids with specific genotypes.

Potential Applications and Limitations of Organoids

Keung highlights the potential applications of organoids in preclinical drug testing and understanding the functional responses to therapeutics. He presents examples of how organoids derived from patient cells or genetically engineered cells have been used to study the absence or silencing of UBE3A, a gene associated with Angelman Syndrome. Keung also acknowledges the limitations of organoids, such as their inability to fully mature past prenatal stages and the molecular stress they experience in a cell culture environment. He mentions ongoing efforts to improve organoid models, including tissue organization, vascularization, and high-throughput analysis methods.

Conclusion

In conclusion, Keung expresses gratitude to FAST for supporting their work and emphasizes the collaborative nature of the scientific community. He encourages further research and collaboration to enhance the understanding and treatment of Angelman Syndrome. Keung also invites readers to reach out with any questions they may have.