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Open Access Highly Accessed Research article

An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury

Li-Wei Chang1, Andreu Viader2, Nobish Varghese1, Jacqueline E Payton1, Jeffrey Milbrandt2 and Rakesh Nagarajan1*

  • * Corresponding author: Rakesh Nagarajan rakesh@wustl.edu

  • † Equal contributors

Author Affiliations

1 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA

2 Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA

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BMC Genomics 2013, 14:84  doi:10.1186/1471-2164-14-84

Published: 6 February 2013

Abstract

Background

The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets.

Results

In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery.

Conclusions

This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs.

Keywords:
Transcriptional regulatory network; MicroRNA regulatory network; Myelination; Schwann cells