Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

Nature Neuroscience, Год журнала: 2021, Номер 24(3), С. 425 - 436

Опубликована: Фев. 8, 2021

Язык: Английский

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Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

Neuron, Год журнала: 2021, Номер 109(19), С. 3088 - 3103.e5

Опубликована: Сен. 27, 2021

Язык: Английский

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Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans

Neuron, Год журнала: 2021, Номер 109(13), С. 2091 - 2105.e6

Опубликована: Май 28, 2021

Язык: Английский

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Neuroimaging biomarkers define neurophysiological subtypes with distinct trajectories in schizophrenia

Nature Mental Health, Год журнала: 2023, Номер 1(3), С. 186 - 199

Опубликована: Март 22, 2023

Язык: Английский

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A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex

Science, Год журнала: 2024, Номер 384(6698)

Опубликована: Май 23, 2024

The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions domains. Using PsychENCODE publicly available data, we mapped enrichment types genes associated neuropsychiatric disorders discrete

Язык: Английский

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Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia

Nature Neuroscience, Год журнала: 2024, Номер 27(6), С. 1075 - 1086

Опубликована: Апрель 22, 2024

Abstract Human brain organization involves the coordinated expression of thousands genes. For example, first principal component (C1) cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing Allen Brain Atlas revealed two new components gene architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic immune processes, specific cell types cytoarchitectonics, genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Cell BrainSpan), we found that C1–C3 represent generalizable transcriptional programs within cells differentially phased during fetal postnatal development. Autism spectrum disorder schizophrenia were specifically C1/C2 respectively, across neuroimaging, differential genome-wide studies. Evidence converged especially in support C3 as normative program adolescent development, can lead atypical supragranular connectivity people at high risk schizophrenia.

Язык: Английский

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Expanding the genetic architecture of nicotine dependence and its shared genetics with multiple traits

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Ноя. 3, 2020

Abstract Cigarette smoking is the leading cause of preventable morbidity and mortality. Genetic variation contributes to initiation, regular smoking, nicotine dependence, cessation. We present a Fagerström Test for Nicotine Dependence (FTND)-based genome-wide association study in 58,000 European or African ancestry smokers. observe five significant loci, including previously unreported loci MAGI2/GNAI1 (rs2714700) TENM2 (rs1862416), extend reported other traits dependence. Using heaviness index from UK Biobank ( N = 33,791), rs2714700 consistently associated; rs1862416 not associated, likely reflecting dependence features captured by index. Both variants influence nearby gene expression (rs2714700/ MAGI2-AS3 hippocampus; rs1862416/ lung), genes spanning dependence-associated enriched cerebellum. (SNP-based heritability 8.6%) genetically correlated with 18 r g 0.40–1.09) co-morbidities. Our results highlight dependence-specific emphasizing FTND as composite phenotype that expands genetic knowledge smoking.

Язык: Английский

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Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids

Molecular Psychiatry, Год журнала: 2020, Номер 25(11), С. 2695 - 2711

Опубликована: Авг. 7, 2020

Abstract Despite extensive genetic and neuroimaging studies, detailed cellular mechanisms underlying schizophrenia bipolar disorder remain poorly understood. Recent progress in single-cell RNA sequencing (scRNA-seq) technologies enables identification of cell-type-specific pathophysiology. However, its application to psychiatric disorders is challenging because methodological difficulties analyzing human brains the confounds due a lifetime illness. Brain organoids derived from induced pluripotent stem cells (iPSCs) patients are powerful avenue investigate pathophysiological processes. Here, we generated iPSC-derived cerebral monozygotic twins discordant for psychosis. scRNA-seq analysis revealed enhanced GABAergic specification reduced cell proliferation following diminished Wnt signaling patient, which was confirmed forebrain neuronal cells. Two additional twin pairs also excess patients’ neural progenitor With well-controlled background, our data suggest that unbalanced excitatory inhibitory neurons during cortical development underlies psychoses.

Язык: Английский

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Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk

Nature Neuroscience, Год журнала: 2020, Номер 23(4), С. 510 - 519

Опубликована: Март 16, 2020

Язык: Английский

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Neuroinflammation in schizophrenia: the role of nuclear factor kappa B

Translational Psychiatry, Год журнала: 2021, Номер 11(1)

Опубликована: Окт. 14, 2021

Abstract Neuroinflammation, particularly in the dorsolateral prefrontal cortex, is well-established a subset of people with schizophrenia, significant increases inflammatory markers including several cytokines. Yet cause(s) cortical inflammation schizophrenia remains unknown. Clues as to potential microenvironmental triggers and/or intracellular deficits immunoregulation may be gleaned from looking further upstream effector immune molecules transcription factors that control gene expression. Here, we focus on ‘master regulator’ nuclear factor kappa B (NF-κB) and review evidence support NF-κB dysregulation causing or contributing neuroinflammation patients. We discuss utility ‘immune biotyping’ tool analyse immune-related transcripts proteins patient tissue, insights into revealed by biotyping compared studies treating patients single, homogenous group. Though ubiquitous nature presents hurdles for drug development, targeting this key immunoregulator novel repurposed therapeutics relatively underexplored area could aid reducing symptoms active neuroinflammation.

Язык: Английский

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