Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration.
Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration.
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综合转录组和蛋白质组分析确定了椎间盘退变中髓核细胞的新调控网络
DOI：
10.1186/s12920-021-00889-z
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发表时间：
2021-02-03
影响因子：
2.7
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Xu C;Luo S;Wei L;Wu H;Gu W;Zhou W;Sun B;Hu B;Zhou H;Liu Y;Chen H;Ye X;Yuan W
椎间盘退变是腰痛和颈痛的主要原因。研究试图通过转录组学或蛋白质组学分析揭示调控网络。然而，两者都没有完全阐明变性过程的确切机制。由于转录后调控可能通过调节mRNA到蛋白产物的翻译过程来影响基因表达，因此转录组学和蛋白质组学的联合研究可能为椎间盘退变的关键调控网络提供更多的见解。为了获得蛋白质组学和转录组学数据，我们对新分离的髓核细胞进行了无标记蛋白质组学分析，并从Gene Expression Omnibus repository中获得了转录组分析数据。为了确定髓核细胞椎间盘退变的关键调控网络，我们进行了生物信息学分析并建立了蛋白- rna相互作用网络。为了验证候选基因，我们进行了体外实验和免疫化学标记，以确定它们在髓核变性过程中的潜在功能。无标记蛋白质组分析共鉴定出656个蛋白，其中503个蛋白在髓核细胞与退变或正常椎间盘细胞之间差异表达。我们利用已有的髓核转录组学分析数据，整合髓核细胞的蛋白质组学和转录组学数据，建立蛋白- rna相互作用网络，展示椎间盘退变的联合调控网络。在网络中，我们发现9个基因出现了显著变化，其中6个基因（CHI3L1、KRT19、COL6A2、DPT、TNFAIP6和COL11A2）在蛋白和mRNA水平上都出现了一致的变化。进一步的功能分析表明，当改变这些候选基因的表达时，它们可以显著影响髓核细胞的变性。这项研究首次使用蛋白质组学和转录组学分析数据的组合分析来确定椎间盘退变中髓核细胞的新调控网络。我们建立的蛋白质- rna相互作用网络显示了新的调控机制和关键基因，可能在椎间盘退变的发病机制中发挥重要作用。
Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.
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影响因子：
1.8
作者：
Martirosyan NL;Patel AA;Carotenuto A;Kalani MY;Belykh E;Walker CT;Preul MC;Theodore N
通讯作者：
Theodore N
影响因子：
4.6
作者：
Kazezian Z;Gawri R;Haglund L;Ouellet J;Mwale F;Tarrant F;O'Gaora P;Pandit A;Alini M;Grad S
通讯作者：
Grad S
基因表达谱识别人类椎间盘退变的潜在生物标志物
影响因子：
3.4
作者：
Guo W;Zhang B;Li Y;Duan HQ;Sun C;Xu YQ;Feng SQ
通讯作者：
Feng SQ
影响因子：
4.3
作者：
Pereira Fernandes D;Bitar M;Jacobs FMJ;Barry G
通讯作者：
Barry G
影响因子：
9.7
作者：
Kazezian, Zepur;Li, Zhen;Pandit, Abhay
通讯作者：
Pandit, Abhay