(505d) Transcriptome and Methylome Analysis of Distal Spinal Cord Location after Spinal Cord Injury

Spinal cord injury (SCI) is a severely debilitating condition affecting a large percentage of population in the U.S. Recovering SCI patients often have increased risk of developing persistent neuropathic pain and other neurodegenerative conditions beyond the primary lesion center later in their life. The molecular mechanism conferring to the “latent” damages at distal tissues, however, remains elusive. In this study, we aimed to understanding molecular changes conferring abnormal functionality at distal spinal cord (DSC) beyond the lesion center (LC) by combining next generation sequencing (RNA-seq and BS-seq), state-of-the-art super-resolution microscopy and immunofluorescence staining. We assessed changes in transcriptome, methylome and chromatin rearrangement of neurons at DSC 7 day post injury. We observed significant transcriptomic changes primarily enriched in neuroinflammation and synaptogenesis associated pathways. Growth factors that regulate neurogenesis and neuron plasticity, including Egr1, Klf4, and Myc, are also found significantly upregulated. Significant changes were observed in the overall level of DNA 5mC and 5hmC as suggested by our imaging analysis. BS-seq results further confirmed the involvement of DNA methylation changes in regulating cytokine, growth factor and ion channel expression contributing to the observed transcriptomic changes. Collectively, our results provide the essential knowledge base towards understanding transcriptomic and epigenomic mechanism in conferring long-term disease risks at distal tissues away from the primary lesion center and shed light on potential molecular targets that govern the regulatory mechanism at DSC.