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

Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex.
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人类背外侧前额叶皮层转录组尺度的空间基因表达。

DOI:
10.1038/s41593-020-00787-0
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发表时间:
2021-03
影响因子:
25
通讯作者:
Jaffe AE
Jaffe AE
中科院分区:
医学1区
文献类型:
--
作者:
Maynard KR;Collado-Torres L;Weber LM;Uytingco C;Barry BK;Williams SR;Catallini JL 2nd;Tran MN;Besich Z;Tippani M;Chew J;Yin Y;Kleinman JE;Hyde TM;Rao N;Hicks SC;Martinowich K;Jaffe AE

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我们使用10x Genomics Visium平台来定义六层人类背外侧前额叶皮层(DLPFC)中基因表达的空间地形图。我们确定了广泛的层丰富的表达签名,并细化关联到以前的层流标记。我们将我们的层状表达特征叠加到大规模单核RNA测序数据上,增强了表达驱动簇的空间注释。通过整合神经精神障碍基因集,我们显示了与精神分裂症和自闭症谱系障碍相关的基因的差异层富集表达,突出了空间定义表达的临床相关性。然后,我们开发了一个数据驱动的框架来定义空间转录组学数据中的无监督聚类,该框架可以应用于形态结构不像皮质层那样明确的其他组织或大脑区域。最后,我们为科学界创建了一个Web应用程序,以探索这些原始和总结的数据,以增强正在进行的神经科学和空间转录组学研究(http://research.libd.org/spatialLIBD)。
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).
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发表时间: 2015-03
期刊: NATURE GENETICS
影响因子: 30.8
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