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  4. Transcriptomic Approaches to Neural Repair

Transcriptomic Approaches to Neural Repair

The Journal of Neuroscience, 2015 · DOI: 10.1523/JNEUROSCI.2599-15.2015 · Published: October 14, 2015

Regenerative MedicineNeurologyBioinformatics

Simple Explanation

The inability of adult CNS neurons to regenerate axons after injury is a major challenge. Understanding the biological mechanisms shaping the injured nervous system is crucial for developing therapies to promote neural repair. Transcriptomic approaches, which involve high-throughput interrogation of gene expression, are being used to discover novel molecular mechanisms for neural repair. These methods provide a comprehensive view of the complex biology governing axon regeneration. This review highlights current work using transcriptomic approaches to identify regulatory networks in the injured nervous system. It discusses analytical strategies for transcriptomics data, the significance of noncoding RNA networks, and the utility of multiomic data integration.

Study Duration
Not specified
Participants
Multiple mouse strains
Evidence Level
Level 5, Transcriptomic analysis

Key Findings

  • 1
    RNA-Seq technology improves the ability to understand gene expression network regulation, because it can identify isoform-specific gene regulators. This allows defining precise transcription start sites and 3' untranslated regions for each differentially expressed isoform.
  • 2
    CREB serves as an important hub for regeneration, but physiological activation of CREB after injury is insufficient to recruit the network needed to promote robust regeneration. AP-1-controlled genes cooperate with other CREB targets to stimulate regeneration.
  • 3
    Activation of a core transcriptional network, involving interactions between multiple transcription factors, coordinates gene expression to promote axon regeneration after peripheral nerve injury. This network can be targeted by small molecules to promote regeneration in CNS neurons.

Research Summary

Transcriptomic approaches are used to identify molecular mechanisms for neural repair. RNA-Seq technology improves the ability to understand gene expression network regulation. Activation of a core transcriptional network, involving interactions between multiple transcription factors, coordinates gene expression to promote axon regeneration after peripheral nerve injury. Resources for the interpretation of transcriptomics data and its assimilation into a global biological framework are rapidly becoming more comprehensive, sophisticated, and user friendly.

Practical Implications

Drug Discovery

Identification of small molecules that can mimic gene expression programs induced by nerve injury, potentially leading to new therapeutic interventions.

Targeted Therapies

Understanding the specific transcriptional networks and regulatory RNAs involved in regeneration can inform the development of targeted therapies to promote axon growth.

Enhancing Intrinsic Growth Capacity

Identifying the biological mechanisms that enable robust CNS axon regeneration, such as activin signaling, can lead to strategies to selectively increase growth in the injured CNS.

Study Limitations

  • 1
    Extracting biologically meaningful information from large transcriptomic datasets remains a formidable challenge.
  • 2
    Analysis of whole tissue samples can make it difficult to determine whether differential expression results from the activation or repression of transcriptional programs in the cells of interest.
  • 3
    Tools for multi-omic data integration are still in their infancy, and we have far to go before these types of analyses become routine.

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