Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions.

Journal: eNeuro
PMID:

Abstract

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 . 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 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 system is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.

Authors

  • Su-Yi Loh
    Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
  • Thomas Jahans-Price
    School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
  • Michael P Greenwood
    School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
  • Mingkwan Greenwood
    School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
  • See-Ziau Hoe
    Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
  • Agnieszka Konopacka
    School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
  • Colin Campbell
    Intelligent Systems Laboratory, University of Bristol, Bristol BS81UB, UK.
  • David Murphy
    Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
  • Charles C T Hindmarch
    Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.