Transcriptome signature of cellular senescence
Transcriptome signature of cellular senescence
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DOI：
10.1093/nar/gkz555
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发表时间：
2019-08-22
影响因子：
14.9
通讯作者：
Gorospe, Myriam
中科院分区：
文献类型：
--
作者：
Casella, Gabriel;Munk, Rachel;Gorospe, Myriam
细胞衰老是衰老和癌症的一个重要组成部分，细胞衰老是由多种触发因素引起的，包括端粒磨损、大分子损伤和激活的癌基因信号。目前，衰老细胞是通过多种特征的组合存在来鉴定的，如衰老相关蛋白的表达和分泌、DNA损伤和β-半乳糖苷酶活性；不幸的是，这些特征在衰老细胞中既不是独有的，也不是普遍存在的。为了确定可靠的共同衰老标记，我们对复制耗竭、电离辐射或阿霉素暴露以及癌基因HRAS(G12V)表达引发的人二倍体成纤维细胞(WI-38，IMR-90)和内皮细胞(HUVEC，HAEC)引发的八种不同衰老模型进行了RNA测序分析。改变的转录本的交集显示，在所有衰老模型中，50个RNA持续升高，18个RNA持续减少，包括许多编码蛋白质的RNA和一些非编码RNA。我们认为，这些共享的转录组图谱将有助于在体内识别衰老细胞，研究它们在衰老和恶性肿瘤中的作用，并开发针对衰老细胞的治疗策略。
Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damageand signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damageand beta-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across eight diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRAS(G12V). The intersection of the altered transcriptomes revealed 50 RNAs consistently elevated and 18 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some non-coding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancyand the development of strategies to target senescent cells therapeutically.