The Landscape of Gene Expression and Molecular Regulation Following Spinal Cord Hemisection in Rats

The Landscape of Gene Expression and Molecular Regulation Following Spinal Cord Hemisection in Rats
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大鼠脊髓半切后基因表达和分子调控的景观

DOI:
10.3389/fnmol.2019.00287
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发表时间:
2019-11
影响因子:
4.8
通讯作者:
Xiaosong Gu
Xiaosong Gu
中科院分区:
医学2区
文献类型:
--
作者:
Bin Yu;Chun Yao;Yongjun Wang;Susu Mao;Yaxian Wang;Ronghua Wu;Wei Feng;Yanping Chen;Jian Yang;Chengbin Xue;Dong Liu;Fei Ding;Xiaosong Gu

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脊髓损伤(Spinal cord injury,SCI)是一个世界性的临床难题。损伤后脊髓组织的细胞状态和分子表达极其复杂,与功能恢复密切相关。然而,SCI后不同类型细胞中基因表达和调控的时空变化仍不清楚。在这里,我们收集了大鼠脊髓半切后28天内11个时间点的喙部和尾部区域的病变。结合全转录组测序和生物信息学分析,我们确定了损伤和假手术动物脊髓组织之间的差异表达基因(DEG)。SCI后,星形胶质细胞、小胶质细胞、少突胶质细胞、免疫细胞和血管系统中的DEG丰富了显著改变的生物过程。然后,我们确定了动态趋势,在这些过程中使用DEG的平均表达谱。基因表达和选定的生物过程的调控网络也被构建,以说明吻和尾组织之间的复杂差异。最后,我们验证了这些网络中的一些关键基因的表达,包括α-突触核蛋白,血红素加氧酶1,骨形态发生蛋白2,转录激活因子3和白血病抑制因子。总的来说,我们提供了一个全面的基因表达和调控网络,揭示了SCI后发生的关键生物学过程的分子特征,这将拓宽对SCI的理解,促进SCI的临床治疗。
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.
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