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脑内细胞类型特异性基因表达与共表达网络架构。

Brain Cell Type Specific Gene Expression and Co-expression Network Architectures.

机构信息

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

出版信息

Sci Rep. 2018 Jun 11;8(1):8868. doi: 10.1038/s41598-018-27293-5.


DOI:10.1038/s41598-018-27293-5
PMID:29892006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5995803/
Abstract

Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell "signatures," which were well conserved across data sets. We validated that the relative expression of top cell type markers are associated with proxies for cell type proportions in bulk RNA expression data from postmortem human brain samples. We further validated novel marker genes using an orthogonal ATAC-seq dataset. We performed multiscale coexpression network analysis of the single cell data sets and identified robust cell-specific gene modules. To facilitate the use of the cell type-specific genes for cell type proportion estimation and deconvolution from bulk brain gene expression data, we developed an R package, BRETIGEA. In summary, we identified a set of novel brain cell consensus signatures and robust networks from the integration of multiple datasets and therefore transcend limitations related to technical issues characteristic of each individual study.

摘要

阐明脑细胞类型特异性基因表达模式对于更好地理解细胞间通讯如何影响大脑功能和功能障碍至关重要。我们着手比较和对比了过去几年内生成的五个人类和鼠类细胞类型特异性转录组范围 RNA 表达数据集。我们定义了三种衡量脑细胞类型相对表达的指标,包括特异性、富集性和绝对表达,并确定了相应的共识脑细胞“特征”,这些特征在数据集之间得到了很好的保留。我们验证了顶级细胞类型标志物的相对表达与来自死后人脑样本的批量 RNA 表达数据中细胞类型比例的替代指标相关。我们进一步使用正交 ATAC-seq 数据集验证了新的标记基因。我们对单细胞数据集进行了多尺度共表达网络分析,并确定了稳健的细胞特异性基因模块。为了促进使用细胞类型特异性基因从批量大脑基因表达数据中估计细胞类型比例和解卷积,我们开发了一个 R 包,BRETIGEA。总之,我们通过整合多个数据集确定了一组新的大脑细胞共识特征和稳健的网络,因此超越了与每个单独研究相关的技术问题特征的限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/c82354c44fc3/41598_2018_27293_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/66ddce23e953/41598_2018_27293_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/5307b61485ed/41598_2018_27293_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/40b79d0928fb/41598_2018_27293_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/38dc519c78a6/41598_2018_27293_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/fdfbff788951/41598_2018_27293_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/7e1b4f353b39/41598_2018_27293_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/7a25c0f3b1e6/41598_2018_27293_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/73650127362a/41598_2018_27293_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/c82354c44fc3/41598_2018_27293_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/66ddce23e953/41598_2018_27293_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/5307b61485ed/41598_2018_27293_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/40b79d0928fb/41598_2018_27293_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/38dc519c78a6/41598_2018_27293_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/fdfbff788951/41598_2018_27293_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/7e1b4f353b39/41598_2018_27293_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/7a25c0f3b1e6/41598_2018_27293_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/73650127362a/41598_2018_27293_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fd5/5995803/c82354c44fc3/41598_2018_27293_Fig9_HTML.jpg

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本文引用的文献

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Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity.

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[2]
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