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首页> 外文期刊>Cartilage >A Membranome-Centered Approach Defines Novel Biomarkers for Cellular Subtypes in the Intervertebral Disc
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A Membranome-Centered Approach Defines Novel Biomarkers for Cellular Subtypes in the Intervertebral Disc

机译：膜上以膜上的方法为椎间盘中的细胞亚型的新型生物标志物定义

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Objective Lack of specific marker-sets prohibits definition and functional distinction of cellular subtypes in the intervertebral disc (IVD), such as those from the annulus fibrosus (AF) and the nucleus pulposus (NP). Design We recently generated immortalized cell lines from human NP and AF tissues; these comprise a set of functionally distinct clonal subtypes. Whole transcriptome analyses were performed of 12 phenotypically distinct clonal cell lines (4× NP-Responder, 4× NP-nonResponder, 2× AF-Sheet forming, and 2× AF-nonSheet forming). Data sets were filtered for membrane-associated marker genes and compared to literature. Results Comparison of our immortal cell lines to published primary NP, AF, and articular chondrocytes (AC) transcriptome datasets revealed preservation of AF and NP phenotypes. NP-specific membrane-associated genes were defined by comparison to AF cells in both the primary dataset (46 genes) and immortal cell-lines (161 genes). Definition of AF-specific membrane-associated genes yielded 125 primary AF cell and 92 immortal cell-line markers. Overlap between primary and immortal NP cells yielded high-confidence NP-specific marker genes for NP-R ( CLDN11, TMEFF2, CA12, ANXA2, CD44 ) and NP-nR (EFNA1, NETO2, SLC2A1). Overlap between AF and immortal AF subtypes yielded specific markers for AF-S ( COLEC12, LPAR1 ) and AF-nS ( CHIC1 ). Conclusions The current study provides a reference platform for preclinical evaluation of novel membrane-associated cell type–specific markers in the IVD. Future research will focus on their biological relevance for IVD function in development, homeostasis, and degenerate conditions.
机译：目的缺乏特定的标记集禁止椎间盘（IVD）中细胞亚型的定义和功能区分，例如来自环纤维（AF）和细胞核拷贝（NP）的细胞亚型。设计我们最近产生了来自人NP和AF组织的永生化细胞系;这些包括一组功能性不同的克隆亚型。进行整个转录组分析，对12个表型不同的克隆细胞系（4×NP响应器，4×NP-NATRESPONDER，2×AF-SHEET成型，2×AF-NONEHEET形成）进行。对膜相关标记基因过滤数据集并与文献进行比较。结果与发表的原发性NP，AF和关节软骨细胞（AC）转录组数据集的结果比较了AF和NP表型的保存。通过与初级数据集（46基因）和不朽的细胞系（161个基因）的AF细胞进行比较来定义NP特异性膜相关基因。 AF特异性膜相关基因的定义产生125个主AF细胞和92个不朽的细胞系标记物。初级和不朽NP细胞之间的重叠产生高频率的NP特异性标记基因，用于NP-R（CLDN11，TMEFF2，CA12，ANXA2，CD44）和NP-NR（EFNA1，NetO2，SLC2A1）。 AF和不朽AF亚型之间的重叠产生AF-S（COLEC12，LPAR1）和AF-NS（CHIC1）的特异性标记。结论目前的研究为IVD中的新型膜相关细胞类型特异性标记的临床前评价提供了参考平台。未来的研究将侧重于其对IVD功能在开发，稳态和退化条件下的生物相关性。

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