Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Exp Physiol. 2012 Apr;97(4):462-8. doi: 10.1113/expphysiol.2011.059790. Epub 2011 Oct 14.
In order to provide an example of useful interaction between systems biology and computational neuroscience traditions, here we aim to identify the molecular response process through which elevated blood pressure induces a temporal sequence of gene expression changes. This initial response may then continually evolve as an adaptive response, altering central blood pressure set-point control. Our approach involves using a set of 96 quantitative PCR gene assays, which represent the molecular process associated with neuronal responses to angiotensin II type 1 receptor (AT1R) activation. We use this set as a probe to search for the AT1R signalling-triggered expression programme in individual neurons and groups of neurons involved in homeostatic regulation of cardiorespiratory function. Specifically, we focus on tissue samples from the nucleus tractus solitarii, as well as groups of A2 neurons and individual A2 cells within the nucleus tractus solitarii, and in the ventrolateral medulla and central amygdala. We assay these neural samples at rest and in response to elevated blood pressure. Analysis of the resulting high-dimensional data set reveals a remarkable complexity and heterogeneity of the samples and of their response to changes in blood pressure. These results demonstrate differential expression programmes for each anatomically distinct neuronal group and neuronal type. Single-cell expression analysis shows that A2 cells also are variable, and that the subset that responds to blood pressure with elevated Fos expression differs from other A2 cells. We present models of gene regulatory networks and of signalling cascades related to AT1R and broadly discuss the opportunities for valuable interactions between systems biology and computational neuroscience.
为了提供系统生物学和计算神经科学传统之间有益交互的范例，我们旨在确定血压升高诱导基因表达变化时间序列的分子反应过程。这种初始反应可能会作为一种适应性反应不断进化，改变中枢血压设定点控制。我们的方法涉及使用一组 96 个定量 PCR 基因检测，这些检测代表与神经元对血管紧张素 II 型 1 受体 (AT1R) 激活反应相关的分子过程。我们使用这个检测集来搜索与 AT1R 信号触发的个体神经元和参与心肺功能稳态调节的神经元群相关的表达程序。具体来说，我们关注来自孤束核的组织样本，以及孤束核内的 A2 神经元群和单个 A2 细胞，以及腹外侧延髓和中央杏仁核。我们在静息状态和血压升高时检测这些神经样本。对由此产生的高维数据集的分析揭示了样本及其对血压变化反应的显著复杂性和异质性。这些结果表明每个解剖上不同的神经元群和神经元类型都有不同的表达程序。单细胞表达分析表明，A2 细胞也具有变异性，并且用升高的 Fos 表达对血压做出反应的亚群与其他 A2 细胞不同。我们提出了与 AT1R 相关的基因调控网络和信号级联模型，并广泛讨论了系统生物学和计算神经科学之间有价值的交互机会。
