Table_9_The Landscape of Gene Expression and Molecular Regulation Following Spinal Cord Hemisection in Rats.XLS

Spinal cord injury (SCI) is a challenging clinical problem worldwide. The cellular state and molecular expression in spinal cord tissue after injury are extremely complex and closely related to functional recovery. However, the spatial and temporal changes of gene expression and regulation in various cell types after SCI are still unclear. Here, we collected the rostral and caudal regions to the lesion at 11 time points over a period of 28 days after rat hemisection SCI. Combining whole-transcriptome sequencing and bioinformatic analysis, we identified differentially expressed genes (DEGs) between spinal cord tissue from injured and sham-operated animals. Significantly altered biological processes were enriched from DEGs in astrocytes, microglia, oligodendrocytes, immune cells, and vascular systems after SCI. We then identified dynamic trends in these processes using the average expression profiles of DEGs. Gene expression and regulatory networks for selected biological processes were also constructed to illustrate the complicate difference between rostral and caudal tissues. Finally, we validated the expressions of some key genes from these networks, including α-synuclein, heme oxygenase 1, bone morphogenetic protein 2, activating transcription factor 3, and leukemia inhibitory factor. Collectively, we provided a comprehensive network of gene expression and regulation to shed light on the molecular characteristics of critical biological processes that occur after SCI, which will broaden the understanding of SCI and facilitate clinical therapeutics for SCI.

脊髓损伤（Spinal cord injury, SCI）是全球范围内极具挑战性的临床难题。损伤后脊髓组织的细胞状态与分子表达模式极为复杂，且与功能恢复密切相关。然而，脊髓损伤后各类细胞类型中基因表达与调控的时空变化仍未明确。本研究采集了大鼠脊髓半切损伤后28天内11个时间点的损伤灶吻侧与尾侧组织样本。结合全转录组测序与生物信息学分析，我们鉴定出损伤组与假手术组脊髓组织间的差异表达基因（differentially expressed genes, DEGs）。我们从脊髓损伤后星形胶质细胞、小胶质细胞、少突胶质细胞、免疫细胞以及血管系统的差异表达基因中富集得到显著改变的生物学过程。随后，我们通过差异表达基因的平均表达谱解析了这些生物学过程的动态变化趋势。同时，我们还针对筛选出的生物学过程构建了基因表达与调控网络，以阐明吻侧与尾侧组织间的复杂差异。最后，我们验证了这些网络中部分关键基因的表达水平，包括α-突触核蛋白（α-synuclein）、血红素氧合酶1（heme oxygenase 1）、骨形态发生蛋白2（bone morphogenetic protein 2）、激活转录因子3（activating transcription factor 3）以及白血病抑制因子（leukemia inhibitory factor）。综上，本研究提供了一套全面的基因表达与调控网络，阐明了脊髓损伤后关键生物学过程的分子特征，这将加深人们对脊髓损伤的认知，并助力脊髓损伤的临床治疗。