IPRD funded research by Yi Zhou
Brain organoids: The goal of our project is to engineer brain organoids from healthy individuals and pediatric rare disease patients. The source of the organoids will be human induced pluripotent stem cells. Single cell RNA sequencing technology will be used to identify different cell types and cellular and molecular signaling pathways to understand disruptions in cellular processes associated with the disease progression. Identifying the pathway disruptions can become a new platform for identification of drug targets for pediatric rare diseases.
Resources
Q&A with Dr. Zhou:
Q#1: Could you tell me a little bit about brain organoids?
A#1: Brain organoids, also known as mini brains, are three-dimensional tissue structures that are artificially grown in a lab and resemble parts of the human brain. They are created by differentiating human pluripotent stem cells in a self-organizing manner. We can use a combination of chemicals to encourage the cells to form different regions of the brain. Thus, organoids are physiologically relevant in vitro 3D brain models that can help researchers study human brain development and disease processes in a controlled laboratory setting.
Q#2: Where do the brain organoids used in your research come from?
A#2: The brain organoids in our research will be derived from either wildtype and mutated human induced pluripotent stem cells (hIPSCs). Through effort coordinated by the YWHAG foundation, a biotech company, Transcripta Bio, has recently generated an IPSs line that contains a disease causing differentiating these IPSC into brain cells, we can create organoids that mimic genetic and cellular environment of Developmental and Epileptic Encephalopathies.
Q#3: How do you use brain organoids in your research?
A#3: In our research, we will use brain organoids to study how YWHAG mutations impact brain development and functions. Specifically, we will use electrophysiology to assess neuronal activity and connectivity. In addition, we will use transcriptomics to analyze gene transcriptions. By comparing these data between wildtype and YWHAG mutated organoids, we hope to identify molecular and cellular pathways affected by the mutation, providing insight into disease mechanism and potential therapeutic targets.