Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social communication and behaviors. However, lack of proper human model system to closely recapitulate human-specific pathophysiology of ASD hinders the precise understanding of its etiology and developing therapeutics. In ...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social communication and behaviors. However, lack of proper human model system to closely recapitulate human-specific pathophysiology of ASD hinders the precise understanding of its etiology and developing therapeutics. In this study, to enlarged our knowledge about ASD, we established threehuman induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD)patientsand their family controls, as well as forebrainorganoids. In addition, human iPSCs-derived forebrain organoidsdisease modelswere investigated whether they can be a useful human-based platform for in vitro disease modeling for idiopathic ASD.More than 80% of individuals with ASD is idiopathic and the prevalence rates of ASD are gradually increasing. An increasing body of evidence suggest that animal models could not fully recapitulate the common pathophysiology of ASD, their etiology is completely unknown. Given the heterogeneity of ASD in its etiology and clinical symptom, monogenic syndromic ASD could not be a representative model system for idiopathic ASD for understanding its etiology and finding its therapeutics. Therefore, generating hiPSC lines from idiopathic ASD patients with diverse clinical symptoms could be a useful platform for understanding the underlying mechanism of idiopathic ASD and establishing patient-specific drug discovery for idiopathic ASD patients. Human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD) patients through forced expression of OCT4, SOX2, KLF4, and c-MYC. The hiPSC lines displayed morphology, gene expression patterns, and pluripotential differentiation potentials similar to those of human embryonic stem cells (hESCs). The hiPSC lines from idiopathic ASD patients might be useful to unveil the underlying mechanism of idiopathic ASD and finding its therapeutics. VIIIMacrencephaly, also called macrocephaly, a growth development disorder in which the brain is abnormally large. There are several neuropsychiatric disorders linked with macrocephaly,however, studies have shown that autism is the most prevalent association with the malformation of MEG. ASD with macrocephaly phenotype show increased cell proliferation and decreased neuron differentiation,but there isless study could recapitulate the mechanism of macrocephaly.In our study, we generated ASD-patient derived forebrain organoidsthat recapitulate macrocephaly phenotype, showing increased cell proliferation and decreased neuron differentiation.Taken together, using hiPSC lines from idiopathic ASD patients generated forebrainorganoidscould be a useful human-based platform for disease modeling.Forebrainorganoidsrecapitulate the human fetal cortical development,increased proliferation rate and delayed neuron differentiation in the ASD organoids, also show macrocephaly phenotype.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects social communication and behaviors. However, lack of proper human model system to closely recapitulate human-specific pathophysiology of ASD hinders the precise understanding of its etiology and developing therapeutics. In this study, to enlarged our knowledge about ASD, we established threehuman induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD)patientsand their family controls, as well as forebrainorganoids. In addition, human iPSCs-derived forebrain organoidsdisease modelswere investigated whether they can be a useful human-based platform for in vitro disease modeling for idiopathic ASD.More than 80% of individuals with ASD is idiopathic and the prevalence rates of ASD are gradually increasing. An increasing body of evidence suggest that animal models could not fully recapitulate the common pathophysiology of ASD, their etiology is completely unknown. Given the heterogeneity of ASD in its etiology and clinical symptom, monogenic syndromic ASD could not be a representative model system for idiopathic ASD for understanding its etiology and finding its therapeutics. Therefore, generating hiPSC lines from idiopathic ASD patients with diverse clinical symptoms could be a useful platform for understanding the underlying mechanism of idiopathic ASD and establishing patient-specific drug discovery for idiopathic ASD patients. Human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD) patients through forced expression of OCT4, SOX2, KLF4, and c-MYC. The hiPSC lines displayed morphology, gene expression patterns, and pluripotential differentiation potentials similar to those of human embryonic stem cells (hESCs). The hiPSC lines from idiopathic ASD patients might be useful to unveil the underlying mechanism of idiopathic ASD and finding its therapeutics. VIIIMacrencephaly, also called macrocephaly, a growth development disorder in which the brain is abnormally large. There are several neuropsychiatric disorders linked with macrocephaly,however, studies have shown that autism is the most prevalent association with the malformation of MEG. ASD with macrocephaly phenotype show increased cell proliferation and decreased neuron differentiation,but there isless study could recapitulate the mechanism of macrocephaly.In our study, we generated ASD-patient derived forebrain organoidsthat recapitulate macrocephaly phenotype, showing increased cell proliferation and decreased neuron differentiation.Taken together, using hiPSC lines from idiopathic ASD patients generated forebrainorganoidscould be a useful human-based platform for disease modeling.Forebrainorganoidsrecapitulate the human fetal cortical development,increased proliferation rate and delayed neuron differentiation in the ASD organoids, also show macrocephaly phenotype.
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