Inter-individual genetic variation has been identified as an important modulator of disease susceptibility, such that different individuals show heterogeneous responses to disease risk factors. Modelling the contribution of human genetic background to phenotypes is limited by the necessity of using human models, and the difficulty of scaling these systems to represent many individuals. Here, we present human brain “Chimeroids”, a highly reproducible, multi-donor brain organoid model that allows co-development of human cerebral cortex from a panel of individuals in a single organoid, while maintaining developmental features similar to endogenous tissue. We leveraged this Chimeroid system to investigate susceptibility across multiple individuals to developmental exposure to neurotoxic stressors showing that individual donors vary in both the penetrance of the effect on target cell types, and the molecular phenotype within each affected cell type. Our system shows that human genetic background is an important mediator of neurotoxin susceptibility, and introduce Chimeroids as a scalable system for high-throughput investigation of the contribution of diverse genetic backgrounds to brain function and disease.
Organized by: Clara Muñoz Castro (RCC Postdoctoral Researcher at Massachusetts General Hospital (Alzheimer’s Disease Research Unit), Harvard Medical School)
Speakers: Noelia Antón Bolaños (PhD; Department of Stem Cell & Regenerative Biology, Harvard University, Cambridge, MA, USA) & Irene Faravelli (PhD; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA)
Sponsor: RCCHU; Harvard University; Stanley Center for Psychiatric Research
LOCATION:RCCHU Conference Room, 26 Trowbridge St. STATUS:CONFIRMED DTSTART:20230411T220000Z DTEND:20230411T230000Z END:VEVENT END:VCALENDAR