RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair Pathways

Author:

Welleford Andrew S.123,Quintero Jorge E.1243,Seblani Nader El1253ORCID,Blalock Eric12,Gunewardena Sumedha6,Shapiro Steven M.78,Riordan Sean M.7,Huettl Peter12,Guduru Zain9,Stanford John A.8,van Horne Craig G.124,Gerhardt Greg A.1249

Affiliation:

1. Department of Neuroscience, University of Kentucky Medical Center, Lexington, KY, USA

2. Brain Restoration Center, University of Kentucky, Lexington, KY, USA

3. * These are co-first authors and have contributed equally to this article

4. Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY, USA

5. Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA

6. Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, KS, USA

7. Division of Neurology, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA

8. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, KS, USA

9. Department of Neurology, University of Kentucky Medical Center, Lexington, KY, USA

Abstract

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson’s disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another section of the nerve fascicles of the distal and pre-degenerated stump of the nerve was dissected and processed for RNA-seq studies. An initial analysis between the pre-lesion status and the postinjury gene expression revealed 3,641 genes that were significantly differentially expressed. In addition, the results support a clear transdifferentiation process that occurred by the end of the 2-wk postinjury. Gene ontology (GO) and hierarchical clustering were used to identify the major signaling pathways affected by the injury. In contrast to previous nonclinical studies, important changes were observed in molecular pathways related to antiapoptotic signaling, neurotrophic factor processes, cell motility, and immune cell chemotactic signaling. The results of our current study provide new insights regarding the essential interactions of different molecular pathways that drive neuronal repair and axonal regeneration in humans.

Funder

Kansas Intellectual and Developmental Disabilities Research Center

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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