Journal ArticleNat Commun · August 9, 2024
One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism ri ...
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Journal ArticleMol Neurodegener · June 11, 2024
BACKGROUND: LRRK2-targeting therapeutics that inhibit LRRK2 kinase activity have advanced to clinical trials in idiopathic Parkinson's disease (iPD). LRRK2 phosphorylates Rab10 on endolysosomes in phagocytic cells to promote some types of immunological res ...
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Journal ArticleScience · October 13, 2023
We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, inter ...
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Journal ArticleJ Clin Invest · March 15, 2023
Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit i ...
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Journal ArticleActa Neuropathol · November 2022
Multiple sclerosis (MS) is a multifocal and progressive inflammatory disease of the central nervous system (CNS). However, the compartmentalized pathology of the disease affecting various anatomical regions including gray and white matter and lack of appro ...
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Journal ArticleProc Natl Acad Sci U S A · July 26, 2022
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, ...
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Journal ArticleNature · December 2020
Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin1,2. However, the mechanism leading to TDP-43 proteinopathy remains unclear. H ...
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Journal ArticleCell · August 6, 2020
Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligod ...
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Journal ArticleMol Autism · May 27, 2020
BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implica ...
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Journal ArticleMol Neurobiol · May 2020
Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism corte ...
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Journal ArticleCell Stem Cell · January 2, 2020
Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a referenc ...
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Journal ArticleNature · September 2019
Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single- ...
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Journal ArticleNat Commun · June 21, 2019
The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neuroge ...
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Journal ArticleScience · May 17, 2019
Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by a ...
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Journal ArticleNeuron · April 3, 2019
In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physi ...
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Journal ArticleScience · December 8, 2017
Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in the emerging tissues. We identified discrete cell type ...
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Journal ArticleMol Cell Neurosci · December 2017
Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currentl ...
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Journal ArticleWorld J Biol Psychiatry · September 2017
OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRN ...
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Journal ArticleJ Neurosci · May 10, 2017
What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is suffic ...
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Journal ArticleJCI Insight · March 23, 2017
Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve ...
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Chapter · 2017
Deep-RACE (or RACEseq) is a recently described method (Olivarius et al. BioTechniques 46(2):130-132, 2009) that applies next-generation sequencing to the Rapid Amplification of cDNA End (RACE) protocol to define the 5' and 3' ends of RNA transcripts. Conve ...
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Chapter · 2017
Transcriptomic as well as in vivo studies have revealed the importance of several lncRNAs in many complex diseases including cancer, cardiovascular, and neurological disorders. In this protocol, we describe how to perform RNAseq data analysis to identify l ...
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Journal ArticleEur J Neurosci · November 2016
Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of spec ...
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Journal ArticleMol Cell Neurosci · July 2016
Triplet repeat expansions in the Fragile X mental retardation 1 (FMR1) gene cause either intellectual disability and autism, or adult-onset neurodegeneration, with poorly understood variability in presentation. Previous studies have identified several long ...
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Journal ArticleBMC Genomics · January 13, 2016
BACKGROUND: Next generation sequencing (NGS) technologies are indispensable for molecular biology research, but data analysis represents the bottleneck in their application. Users need to be familiar with computer terminal commands, the Linux environment, ...
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Journal ArticleCurr Alzheimer Res · 2016
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by welldefined neuropathological brain changes including amyloid plaques, neurofibrillary tangles and the presence of chronic neuroinflammation. OBJECTIVE: The br ...
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Journal ArticleProc Natl Acad Sci U S A · December 29, 2015
Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of ...
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Journal ArticleJ Biol Chem · May 22, 2015
Set-β protein plays different roles in neurons, but the diversity of Set-β neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-β are altered in Alzheimer disease, cleavage of Set-β leads to ...
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Journal ArticleJ Alzheimers Dis · 2015
The underlying genetic variations of late-onset Alzheimer's disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD ...
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Journal ArticleFront Genet · 2015
CGG repeat expansions in the Fragile X mental retardation 1 (FMR1) gene are responsible for a family of associated disorders characterized by either intellectual disability and autism Fragile X Syndrome (FXS), or adult-onset neurodegeneration Fragile X-ass ...
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Journal ArticleMol Ther Nucleic Acids · November 18, 2014
Non-protein coding RNAs (ncRNAs) make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an imp ...
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Journal ArticleThe FASEB Journal · April 2014
Ocular surface is continuously exposed to particles, microorganisms and other stressors. To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on ident ...
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Journal ArticlePLoS One · 2014
PURPOSE: To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors. METHODS: Total RNA from the mouse cornea was subjected to next-g ...
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Journal ArticleMol Autism · September 4, 2013
BACKGROUND: Autism spectrum disorders (ASD) manifest with neurodevelopmental phenotypes including communicative, social and behavioral impairments that affect as many as 1 in 88 children. The majority of autism cases have no known genetic cause, suggesting ...
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Journal ArticleEur J Neurosci · June 2013
Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age-related cognitive deficits. Restriction of calorie intake and prolonged treatment ...
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