Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex
| Autor: | Stephen R. Williams, Zachary Besich, Matthew N. Tran, Joseph L. Catallini, Yifeng Yin, Cedric Uytingco, Nikhil Rao, Lukas M. Weber, Thomas M. Hyde, Kristen R. Maynard, Stephanie C. Hicks, Madhavi Tippani, Keri Martinowich, Jennifer Chew, Andrew E. Jaffe, Leonardo Collado-Torres, Brianna K. Barry, Joel E. Kleinman |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene regulatory network Gene Expression Prefrontal Cortex Genomics Computational biology Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Gene expression medicine Humans Gene Regulatory Networks Gene General Neuroscience medicine.disease Dorsolateral prefrontal cortex 030104 developmental biology medicine.anatomical_structure Expression (architecture) Autism spectrum disorder Schizophrenia Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | We used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. 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 then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research (http://research.libd.org/spatialLIBD). |
| Databáze: | OpenAIRE |
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