Abstract:
Extracellular matrix remodeling is a hallmark of tissue development, homeostasis, and disease. The processes that mediate remodeling, and the consequences of such, are the topic of extensive focus in biomedical research. Cell culture methods represent a crucial tool utilized by those interested in matrisome function, the easiest of which are implemented with immortalized/cancer cell lines. These cell lines often form the foundations of a research proposal, or serve as vehicles of validation for other model systems. For these reasons, it is important to understand the complement of matrisome genes that are expressed when identifying appropriate cell culture models for hypothesis testing. To this end, we harvested bulk RNA sequencing data from the Cancer Cell Line Encyclopedia (CCLE) to assess matrisome gene expression in 1019 human cell lines. Our examination reveals that a large proportion of the matrisome is poorly represented in human cancer cell lines, with approximately 10% not expressed above threshold in any of the cell lines assayed. Conversely, we identify clusters of essential/common matrisome genes that are abundantly expressed in cell lines. To validate these observations against tissue data, we compared our findings with bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) portal and The Cancer Genome Atlas (TCGA) program. This comparison demonstrates general agreement between the \"essential/common\" and \"dark/uncommon\" matrisome across the three datasets, albeit with discordance observed in 59 matrisome genes between cell lines and tissues. Notably, all of the discordant genes are essential/common in tissues yet minimally expressed in cell lines, underscoring critical considerations for matrix biology researchers employing immortalized cell lines for their investigations.
摘要:
细胞外基质重塑是组织发育的标志,稳态,和疾病。介导重塑的过程,以及这样的后果,是生物医学研究中广泛关注的话题。细胞培养方法代表了那些对母系功能感兴趣的人使用的关键工具,其中最简单的是用永生化/癌细胞系实现的。这些细胞系通常构成研究计划的基础,或作为其他模型系统的验证工具。由于这些原因,在鉴定合适的细胞培养模型进行假设检验时,了解所表达的基质基因的互补序列是很重要的.为此,我们从癌细胞系百科全书(CCLE)收集大量RNA测序数据,以评估1019种人细胞系中的基质基因表达.我们的检查显示,在人类癌细胞系中,大部分的配系物表现不佳,在任何测定的细胞系中,约有10%的表达量未超过阈值。相反,我们鉴定了在细胞系中大量表达的必需/常见的母系基因簇。为了根据组织数据验证这些观察结果,我们将我们的发现与来自基因型-组织表达(GTEx)门户和癌症基因组图谱(TCGA)程序的大量RNA测序数据进行了比较.此比较表明,在三个数据集中,“基本/常见”和“黑暗/不常见”矩阵之间存在普遍共识,尽管在细胞系和组织之间的59个母系基因中观察到不一致。值得注意的是,所有不一致的基因在组织中是必需的/共同的,但在细胞系中最低限度地表达,强调使用永生化细胞系进行研究的基质生物学研究人员的关键考虑因素。