Microgenomics 2021 webinar : Cerebral organoids: creating a solid foundation to study human disease скачать в хорошем качестве

Microgenomics 2021 webinar : Cerebral organoids: creating a solid foundation to study human disease

Amanda Kedaigle is a Computational Biologist at the Broad Institute and Harvard University, working with the groups of Paola Arlotta, Joshua Levin, and Aviv Regev. Her research leverages transcriptomic and epigenomic data from brain organoids to gain insight into human development and psychiatric disorders. She received her Ph.D. in Computational and Systems Biology from MIT in 2018, where she applied novel tools combining 'omic data modalities to the study of Huntington's Disease, in the lab of Ernest Fraenkel. She also holds a Graduate Education in Medical Sciences certification from the Institute for Medical Engineering and Science, and a B.A. in Bioinformatics from Wellesley College. Her talk will be focused on evaluating the reproducibility and fidelity of human brain organoids using single cell data. Neurodevelopmental disorders are difficult to study due to practical and ethical concerns in human studies, and the vast differences between developmental processes in human brain compared to common model organisms. Cerebral organoids are three-dimensional in vitro models of human brain organogenesis, which have been shown to produce a large diversity of cell types resembling those in the human developing cortex. However, realizing the full potential of these tools requires a deep understanding of the model: the cell types produced, their developmental trajectories, the reproducibility between batches and organoids, and any differences from endogenous cells. Here, using a large single-cell atlas of organoid development, we evaluate their reproducibility and fidelity over time. Finally, we demonstrate the utility of these highly reproducible organoids by evaluating the molecular and cellular effects of mutations in genes which have been associated with Autism Spectrum Disorder. The work provides a comprehensive, single-cell molecular map of human corticogenesis in organoids, identifying consistent molecular programs of cellular diversification, and elucidating novel functions for genes important to human neurodevelopment.