后纵韧带骨化症是常见的退行性脊柱疾病，异常骨化的后纵韧带压迫脊髓和神经根，进而导致严重的神经功能障碍。其发病机理目前未知，导致其难以诊断和治疗。前人的研究得到了多个基因组位点，但是后纵韧带骨化症的致病基因仍未可知。不仅如此，后纵韧带骨化症的全转录组表达谱仍是一片空白。为了获取最接近病变环境的转录组，本课题组拟采用未经过原代培养以及诱导分化的间充质干细胞为载体，同时搭配单细胞测序技术来探究整个转录组的变化。与此同时，为了获取更加全面的基因组变化，本课题组拟采用全基因组测序的方法，并与转录组的变化进行整合分析。通过一系列的数据挖掘和生物信息分析方法，鉴定致病基因。最后，本课题组拟利用基因打靶、基因过表达等技术验证致病基因的生物学功能。本课题组创新性的同时测定全基因组与全转录组，并通过一系列数据挖掘方法，鉴定致病基因，研究致病通路，为揭示的后纵韧带骨化症发生发展奠定坚实基础。

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder that results from ectopic ossification of the posterior longitudinal ligament, compressing the spinal cord and nerve root, leading to intractable neurological disorders. Without the pathogenesis, the diagnosis and treatment remain challenging. Previous studies have identified multiple loci associated with OPLL; however, susceptibility genes in these loci have not been identified yet. What’s more, the transcriptome of OPLL remains blank. To obtain the transcriptome capable of reflecting the OPLL’s etiology, we intend to use the mesenchymal stem cells (MSCs) to perform single cell RNA sequencing. In the meantime, we will perform whole genome sequencing (WGS) to obtain the most comprehensive genetic information change during the OPLL. By integrating the change of transcriptome and genome using bioinformatics analysis like data mining, we would be able to identify the genes causing OPLL. In the last, we intent to utilize techniques like gene knock-out and over-expression to validate the functions of identified genes. In summary, we will integrate the changes of genome and transcriptome to identify the susceptibility genes, and investigate the pathways involved in OPLL, thus providing new insight into the mechanism of OPLL.