Brain organoids: the quest to crack human cortical development and disease

Ana Uzquiano López, PhD  
Postdoctoral Research Fellow
Department of Stem Cell and Regenerative Biology
Harvard University
Boston, MA, USA 

This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS3), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

In person : 
IRCM Auditorium Jacques-Genest
110, avenue des Pins O, H2W 1R7 Montreal

About this conference : 

Brain organoids present an experimental system to study how human brain cell diversity is produced and investigate species-specific developmental processes that are difficult to access in utero. However, realizing the utility for these models to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events of the embryonic human developing cortex. Here, we generated a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We leveraged these data to define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. Based on this latter finding, we are now further leveraging cortical organoids to explore the mechanistic underpinning of callosal projection neuron expansion and diversification in the human cerebral cortex. In parallel, we have capitalized on the human cortical organoid atlas to identify abnormalities in the developmental trajectories of cortical cells when the ASD-risk gene PTEN in mutated. In sum, our work provides a comprehensive, single-cell molecular map of cortical organoid development, and validates this atlas of human corticogenesis in vitro as a resource to prime investigation into mechanisms of human cortical development and disease. 

About  Ana Uzquiano López : 
I studied Biology in Madrid, followed by pursuing a master with a strong focus on neurodevelopment in London. For my thesis, I joined the lab of Dr. Fiona Francis where, through the use of mouse models, I investigated molecular and cellular mechanisms at the basis of cortical malformations, also affecting human patients. Driven by a strong interest in deciphering human-specific features of brain development, I joined the lab of Dr. Paola Arlotta in Harvard in 2019. Since then, I have been using brain organoids to understand how human neurons are made and to decipher the biological basis of neurodevelopmental disorders.