Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations.
Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations.
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DOI：
10.3390/cells10113126
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发表时间：
2021-11-11
期刊：
影响因子：
6
通讯作者：
Kosinsky RL
中科院分区：
文献类型：
--
作者：
Saul D;Kosinsky RL
人类的衰老过程与分子变化和细胞退化有关，导致癌症发病率随年龄增长而显著增加。尽管它们之间存在潜在的相关性，但癌症和衰老相关的转录变化之间的关系在很大程度上是未知的。在这项研究中，我们的目的是分析慢性粒细胞白血病（CML），结直肠癌（CRC），肝细胞癌（HCC），肺癌（LC）和胰腺导管腺癌（PDAC）的公开可用的批量mRNA-seq和单细胞RNA-seq（scRNA-seq）数据集中与衰老相关的转录模式。事实上，我们检测到与健康对照样品相比，各种衰老/衰老诱导基因（ASIG）在恶性疾病中上调。为了阐明ASIG在细胞发育过程中的重要性，进行了伪时间分析，其揭示了不同癌症特异性ASIG特征的晚期富集。值得注意的是，我们能够证明本研究中分析的所有癌症实体都包含表达ASIG的细胞群。虽然在PDAC中ASIG和全转录组变化之间仅检测到微小的相关性，但在CML、CRC、HCC和LC样品中诱导了高比例的ASIG。这些独特的细胞亚群可以作为未来研究衰老和衰老在人类恶性肿瘤中作用的基础。
The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies.
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82.9
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