About this Research Topic
Complex neuropsychiatric disorders represent common and highly debilitating conditions for which efficient treatments are lacking. Recent sequencing efforts and large population studies have associated myriads of genetic markers and risk factors with neuropsychiatric disease. Along with this, significant progress in the generation of human pluripotent stem cell (hPSC)-derived brain organoids - three-dimensional cultures that closely recapitulate early stages of human brain development - have now opened unprecedented opportunities to study the molecular and cellular basis of these conditions. Brain organoids grown with distinct differentiation protocols and exposed to different culture conditions can generate a wide spectrum of brain areas, and reach a growing cellular complexity, maturation and functionality. Moreover, brain organoids generated from various lines with multiple genetic backgrounds, subjected to gene modification, or derived from cells obtained from healthy individuals and patients, enable the ability to precisely link genetic variants with disease-relevant cellular phenotypes.
Despite this versatility and promise, several barriers still exist for these systems to advance our understanding of neuropsychiatric disease. Issues of variability across iPSC lines and genetic backgrounds as well as in organoid generation, together with the limited scalability of these systems, greatly hinder the systematic analysis of the genetic spectrum of these conditions. Furthermore, limited neuronal maturity, irregular spatial topography, lack of key structures such as vasculature and blood brain barrier, and poor representation of functional microglia currently limits their disease modeling capacity. The goal of our special issue is to invite researchers, who are at the forefront of brain organoid research, to contribute their current knowledge and technical advances addressing these barriers and limitations, as well as successful applications of brain organoids to model neuropsychiatric disease.
This Research Topic will feature recent advances and findings using brain organoids as a model system to inform the underlying molecular and cellular etiology of complex neuropsychiatric disorders, including but not limited to intellectual disability, schizophrenia, autism spectrum disorders (ASDs), Tourette syndrome, bipolar disorders, Attention-Deficit/Hyperactivity Disorder (ADHD), Obsessive-compulsive disorder (OCD), major depression, and anxiety disorders. Studies examining the mechanisms of disease (genetic, epigenetic and gene x environment interactions), as well as methodological advancements (biomaterials/biomolecules, microdevices, and novel methods, etc.) aimed at improving the quality and applicability of brain organoids as a disease model will be considered. Studies that address intra- and inter-organoid variability in using donor-derived iPSC lines are also welcome. Original research articles, method-driven papers, reviews, and perspectives can be submitted under this Topic.
Despite this versatility and promise, several barriers still exist for these systems to advance our understanding of neuropsychiatric disease. Issues of variability across iPSC lines and genetic backgrounds as well as in organoid generation, together with the limited scalability of these systems, greatly hinder the systematic analysis of the genetic spectrum of these conditions. Furthermore, limited neuronal maturity, irregular spatial topography, lack of key structures such as vasculature and blood brain barrier, and poor representation of functional microglia currently limits their disease modeling capacity. The goal of our special issue is to invite researchers, who are at the forefront of brain organoid research, to contribute their current knowledge and technical advances addressing these barriers and limitations, as well as successful applications of brain organoids to model neuropsychiatric disease.
This Research Topic will feature recent advances and findings using brain organoids as a model system to inform the underlying molecular and cellular etiology of complex neuropsychiatric disorders, including but not limited to intellectual disability, schizophrenia, autism spectrum disorders (ASDs), Tourette syndrome, bipolar disorders, Attention-Deficit/Hyperactivity Disorder (ADHD), Obsessive-compulsive disorder (OCD), major depression, and anxiety disorders. Studies examining the mechanisms of disease (genetic, epigenetic and gene x environment interactions), as well as methodological advancements (biomaterials/biomolecules, microdevices, and novel methods, etc.) aimed at improving the quality and applicability of brain organoids as a disease model will be considered. Studies that address intra- and inter-organoid variability in using donor-derived iPSC lines are also welcome. Original research articles, method-driven papers, reviews, and perspectives can be submitted under this Topic.
Keywords: Organoids, stem cells, neuropsychiatric disorders, genetic, risk factors
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