Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions.
Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions.
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DOI：
10.1523/eneuro.0243-17.2017
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发表时间：
2017-11
期刊：
影响因子：
3.4
通讯作者：
Hindmarch CCT
中科院分区：
文献类型：
--
作者：
Loh SY;Jahans-Price T;Greenwood MP;Greenwood M;Hoe SZ;Konopacka A;Campbell C;Murphy D;Hindmarch CCT
视上核（SON）是下丘脑中负责合成和分泌肽类激素血管加压素和催产素的神经元群。生理线索，如脱水，盐负荷和哺乳，SON经历了功能相关的可塑性，我们以前在大鼠中描述的转录组水平。使用无监督图形套索（Glasso）算法，我们从500个塑料SON基因中重建了一个假定的网络，其中基因是节点，边缘是推断的相互作用。在网络中鉴定的最活跃的节点基因是Caprin2。Caprin2编码一种RNA结合蛋白，我们以前已经证明，这种蛋白对大鼠下丘脑SON中神经内分泌调节神经元的功能至关重要。为了测试Glasso网络的有效性，我们在分化的大鼠嗜铬细胞瘤PC12细胞中过表达或敲低Caprin2转录物，并表明这些操作对推定的靶mRNA水平具有显著的相反影响。这些研究表明，Glasso算法在体内系统中的预测能力是准确的，并确定了可能对SON的功能可塑性很重要的生物靶点。
The supraoptic nucleus (SON) is a group of neurons in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised graphical lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions. The most active nodal gene identified within the network was Caprin2. Caprin2 encodes an RNA-binding protein that we have previously shown to be vital for the functioning of osmoregulatory neuroendocrine neurons in the SON of the rat hypothalamus. To test the validity of the Glasso network, we either overexpressed or knocked down Caprin2 transcripts in differentiated rat pheochromocytoma PC12 cells and showed that these manipulations had significant opposite effects on the levels of putative target mRNAs. These studies suggest that the predicative power of the Glasso algorithm within an in vivo system is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.