Integrated systems analysis reveals conserved gene networks underlying response to spinal cord injury

Jordan W. Squair, Seth Tigchelaar, Kyung Mee Moon, Jie Liu, Wolfram Tetzlaff, Brian K. Kwon, Andrei V. Krassioukov, Christopher R. West, Leonard J. Foster, Michael A. Skinnider

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Spinal cord injury (SCI) is a devastating neurological condition for which there are currently no effective treatment options to restore function. A major obstacle to the development of new therapies is our fragmentary understanding of the coordinated pathophysiological processes triggered by damage to the human spinal cord. Here, we describe a systems biology approach to integrate decades of small-scale experiments with unbiased, genome-wide gene expression from the human spinal cord, revealing a gene regulatory network signature of the pathophysiological response to SCI. Our integrative analyses converge on an evolutionarily conserved gene subnetwork enriched for genes associated with the response to SCI by small-scale experiments, and whose expression is upregulated in a severity-dependent manner following injury and downregulated in functional recovery. We validate the severity-dependent upregulation of this subnetwork in rodents in primary transcriptomic and proteomic studies. Our analysis provides systems-level view of the coordinated molecular processes activated in response to SCI.

Original languageEnglish (US)
Article numbere39188
JournaleLife
Volume7
DOIs
StatePublished - Oct 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience

Fingerprint

Dive into the research topics of 'Integrated systems analysis reveals conserved gene networks underlying response to spinal cord injury'. Together they form a unique fingerprint.

Cite this