From neurodevelopmental to neurodegenerative disorders, brain disorders often pose an immense, growing challenge for affected individuals, families, communities, and societies. Effective therapeutic options are limited and primarily non-existent. Genome wide association studies and transcriptomic analyses have revealed an interconnected web of various genetic risk factors across brain disorders that underlines the complexity and sluggish pace in elucidating these disorders. Brian region and cell type specificity further complicate the understanding of brain disorder etiology and pathogenesis. Human stem cell derived brain organoids have provided a platform for relating human-specific genetic variability to cell-type specificity in the investigation of brain disorders. Although two-dimensional PSC-derived neural cultures recapitulate some organizational and transcriptomic aspects of early brain development while preserving donor-specific genetic background, three-dimensional brain organoids demonstrate more complex cytoarchitecture including human-specific outer radial glia cell organization in outer subventricular-like zones, advanced spatiotemporal transcriptomics of brain development across various cell types up to approximately day 60 of brain development, and brain region interconnectivity. Brain organoids provide a powerful model to investigate mechanisms of neurodevelopmental and adult brain disorders.
Limited access to human brain development presents a challenge to understanding mechanisms of human neurodevelopmental disorders. Brain organoids have provided access to some aspects of human brain development that could be dysregulated and contributing to the establishment of neurodevelopmental disorders and subsequent behaviors. However, a key question remains outstanding; how much of adult and age-related brain disorders are foreshadowed in early brain development and can brain organoids reveal this underlying biology? Additionally, are there specific mechanisms, pathways or homeostatic processes that can be perturbed to induce aging-related brain pathologies in brain organoids which typically model processes of early brain development?
This research topic explores the potential of brain organoids to model not only the etiology of brain disorders but also pathogenesis, including neurodegeneration throughout aging and subsequent brain atrophy. We welcome original research articles, reviews, methods, opinions, and letters related to the relevance of and advancements in brain organoid technology to model brain disorders with origins in brain development, like schizophrenia and autism spectrum disorder, and those associated with aging and neurodegeneration, including but not limited to Alzheimer’s disease and Parkinson’s disease. We hope that this topic highlights the advantages, challenges, and future directions of brain organoids in disease modeling and therapeutic development.
From neurodevelopmental to neurodegenerative disorders, brain disorders often pose an immense, growing challenge for affected individuals, families, communities, and societies. Effective therapeutic options are limited and primarily non-existent. Genome wide association studies and transcriptomic analyses have revealed an interconnected web of various genetic risk factors across brain disorders that underlines the complexity and sluggish pace in elucidating these disorders. Brian region and cell type specificity further complicate the understanding of brain disorder etiology and pathogenesis. Human stem cell derived brain organoids have provided a platform for relating human-specific genetic variability to cell-type specificity in the investigation of brain disorders. Although two-dimensional PSC-derived neural cultures recapitulate some organizational and transcriptomic aspects of early brain development while preserving donor-specific genetic background, three-dimensional brain organoids demonstrate more complex cytoarchitecture including human-specific outer radial glia cell organization in outer subventricular-like zones, advanced spatiotemporal transcriptomics of brain development across various cell types up to approximately day 60 of brain development, and brain region interconnectivity. Brain organoids provide a powerful model to investigate mechanisms of neurodevelopmental and adult brain disorders.
Limited access to human brain development presents a challenge to understanding mechanisms of human neurodevelopmental disorders. Brain organoids have provided access to some aspects of human brain development that could be dysregulated and contributing to the establishment of neurodevelopmental disorders and subsequent behaviors. However, a key question remains outstanding; how much of adult and age-related brain disorders are foreshadowed in early brain development and can brain organoids reveal this underlying biology? Additionally, are there specific mechanisms, pathways or homeostatic processes that can be perturbed to induce aging-related brain pathologies in brain organoids which typically model processes of early brain development?
This research topic explores the potential of brain organoids to model not only the etiology of brain disorders but also pathogenesis, including neurodegeneration throughout aging and subsequent brain atrophy. We welcome original research articles, reviews, methods, opinions, and letters related to the relevance of and advancements in brain organoid technology to model brain disorders with origins in brain development, like schizophrenia and autism spectrum disorder, and those associated with aging and neurodegeneration, including but not limited to Alzheimer’s disease and Parkinson’s disease. We hope that this topic highlights the advantages, challenges, and future directions of brain organoids in disease modeling and therapeutic development.