Comparative analysis of the transcriptome of injured nerve segments reveals spatiotemporal responses to neural damage in mice

Abstract

Nerves are particularly vulnerable to damage due to their unique structure with meter-long axons. In the peripheral nervous system neurons and Schwann cells can activate the injury-response program that directs axons to either regenerate or degenerate after traumatic nerve injury. However, the differences between the genetic programs driving nerve regeneration and degeneration have not yet been described extensively. To understand these differences, in this study we have compared the injury-induced transcriptomic changes between the regenerating proximal segment and the degenerating distal segment of a transected nerve, at different post-injury time points. We analyzed the spatiotemporal dynamics of the mouse transcriptome using a sciatic nerve-injury model by means of RNA sequencing. The results of the differentially regulated genes (DEGs) analysis show that some DEG groups are similarly regulated in both proximal and distal segments, and primarily display a positive correlation. However, some DEG groups are exclusively regulated in either the proximal or the distal segment, suggesting that these DEG groups constitute a genetic network for distinguishing the regenerative and degenerative responses. In addition, our gene ontology analysis revealed an enrichment of particular biological processes in different phases and locations. Thus, our data provide a spatiotemporal profile of the transcriptomes that are differentially regulated in either regenerating or degenerating nerves, in vivo. The specific biological processes enriched in the DEG groups might delineate the injury-responsive program that induces contrasting regenerative and degenerative responses in different nerve segments.