Profiling gene expression in the human dentate gyrus granule cell layer reveals insights into schizophrenia and its genetic risk.
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The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing.
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dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Dendritic spine alterations in schizophrenia. Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia. Single-nucleus and single-cell transcriptomes compared in matched cortical cell types. Genetic identification of brain cell types underlying schizophrenia. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Single-cell transcriptomic analysis of Alzheimer’s disease. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. A survey of human brain transcriptome diversity at the single cell level. Single-cell genomics identifies cell type-specific molecular changes in autism. Conserved cell types with divergent features in human versus mouse cortex. Layer- and cell type-specific modulation of excitatory neuronal activity in the neocortex. Cell type-specific structural organization of the six layers in rat barrel cortex. The neocortical circuit: themes and variations. The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Last, we created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research ( ).ĭeFelipe, J. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions in which morphological architecture is not as well defined as cortical laminae. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially defined expression. We overlaid our laminar expression signatures on large-scale single nucleus RNA-sequencing data, enhancing spatial annotation of expression-driven clusters. We identified extensive layer-enriched expression signatures and refined associations to previous laminar markers. We used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex.