Sci Rep 2018 May 30;8(1):8423. Epub 2018 May 30.
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, 33136, USA.
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Mol Autism 2015 19;6:55. Epub 2015 Oct 19.
Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461 USA ; Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461 USA ; Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461 USA.
Background: Disruptive mutation in the CHD8 gene is one of the top genetic risk factors in autism spectrum disorders (ASDs). Previous analyses of genome-wide CHD8 occupancy and reduced expression of CHD8 by shRNA knockdown in committed neural cells showed that CHD8 regulates multiple cell processes critical for neural functions, and its targets are enriched with ASD-associated genes.
Methods: To further understand the molecular links between CHD8 functions and ASD, we have applied the CRISPR/Cas9 technology to knockout one copy of CHD8 in induced pluripotent stem cells (iPSCs) to better mimic the loss-of-function status that would exist in the developing human embryo prior to neuronal differentiation. Read More
Mol Neurobiol 2017 Aug 29;54(6):4507-4523. Epub 2016 Jun 29.
Laboratory of Clinical and Developmental Genomics, National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 10 Center Drive, MSC 1255, Building 10, Room 1C-250, Bethesda, MD, 20892-1255, USA.
Autism spectrum disorder is a complex neurodevelopmental disorder whose pathophysiology remains elusive as a consequence of the unavailability for study of patient brain neurons; this deficit may potentially be circumvented by neural differentiation of induced pluripotent stem cells. Rare syndromes with single gene mutations and autistic symptoms have significantly advanced the molecular and cellular understanding of autism spectrum disorders; however, in aggregate, they only represent a fraction of all cases of autism. In an effort to define the cellular and molecular phenotypes in human neurons of non-syndromic autism, we generated induced pluripotent stem cells (iPSCs) from three male autism spectrum disorder patients who had no identifiable clinical syndromes, and their unaffected male siblings and subsequently differentiated these patient-specific stem cells into electrophysiologically active neurons. Read More
Transl Psychiatry 2017 07 25;7(7):e1179. Epub 2017 Jul 25.
Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary.
The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Read More
Mol Brain 2015 Sep 30;8(1):57. Epub 2015 Sep 30.
Department of Biological Sciences, College of Natural Sciences, Seoul National University, Gwanangno 599, Seoul, Gwanak-gu, 151-747, Korea.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social cognition, language development, and repetitive/restricted behaviors. Due to the complexity and heterogeneity of ASD and lack of a proper human cellular model system, the pathophysiological mechanism of ASD during the developmental process is largely unknown. However, recent progress in induced pluripotent stem cell (iPSC) technology as well as in vitro neural differentiation techniques have allowed us to functionally characterize neurons and analyze cortical development during neural differentiation. Read More