Gene expression data from postnatal cerebellum, prefrontal cortex and liver: comparison on tissue differences (miRNA). Homo sapiens

To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues. Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targets’ expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization. Overall design: Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Agilent Human miRNA Microarray.

为解析分子在成人人体组织功能分化中的作用，我们针对小脑（cerebellum）、前额叶皮层（prefrontal cortex）及肝脏（liver）三种组织，系统性检测了信使RNA（mRNA）、蛋白质、蛋白质磷酸化水平以及微小RNA（miRNA）的表达情况。研究发现，在所有检测维度上，各组织间均呈现显著的特征差异。
进一步分析结果显示，组织间差异表达的miRNA对组织间mRNA的表达仅存在微弱但显著的调控效应，而对蛋白质表达的调控效应则相对更强。值得注意的是，在所研究的三种组织中，miRNA均优先靶向基因调控因子、转录因子及激酶。沿此调控路径进一步分析，我们发现miRNA的调控效应可通过靶标转录因子与激酶的表达变化得到进一步放大，进而引发其下游靶标的表达及磷酸化水平改变。
尤为关键的是，miRNA调控可降低而非提升两个脑区个体间的基因表达变异度。上述发现揭示了miRNA调控互作的复杂性，并与此前提出的miRNA在基因表达渠化（canalization）中的作用假说相符。
实验整体设计：本数据集共纳入9份样本，取自3名成人个体的三种死后人体组织：小脑（cerebellum）、前额叶皮层（prefrontal cortex）及肝脏（liver）。从上述解剖分离的组织中提取的RNA，与安捷伦（Agilent）人类miRNA微阵列芯片完成了杂交反应。