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人类血浆中整个转录组的组成:细胞来源和衰老修饰。

Composition of the whole transcriptome in the human plasma: Cellular source and modification by aging.

机构信息

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Gerontology Research Center, Tampere University, Tampere, Finland.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Gerontology Research Center, Tampere University, Tampere, Finland; Science Centre, Pirkanmaa Hospital District, Tampere, Finland.

出版信息

Exp Gerontol. 2021 Jan;143:111119. doi: 10.1016/j.exger.2020.111119. Epub 2020 Oct 18.

DOI:10.1016/j.exger.2020.111119
PMID:33086079
Abstract

Plasma contains several bioactive molecules (RNA, DNA, proteins, lipids, and metabolites), which are well preserved in extracellular vesicles, that are involved in many types of cell-to-cell interactions, and are capable of modifying biological processes in recipient cells. To obtain information about the source of mRNA molecules present in the plasma, we analyzed the plasma extracellular RNA (exRNA) of healthy individuals using RNA-sequencing and compared it to that of the peripheral blood mononuclear cell (PBMCs) of the same individual. The resultant data indicates that large proportion of the transcripts in plasma are derived from cell types other than PBMCs. To assess aging-associated changes in the plasma exRNA composition, gene ontology enrichment analysis was performed, revealing a functional decline in biological processes as a result of aging. Additionally, plasma RNA levels were analyzed with differential expression analysis, revealing 10 transcripts with significant aging-associated changes. Thus, it seems that the plasma exRNA is not fully derived from the PBMCs. Instead, other cell types supply RNAs to constitute the plasma exRNA compartment. This was true in both the young and elderly individuals that were tested. Furthermore, the RNA content of the plasma showed significant changes due to aging, affecting important biological processes.

摘要

血浆中含有多种生物活性分子(RNA、DNA、蛋白质、脂质和代谢物),这些分子很好地保存在细胞外囊泡中,参与多种类型的细胞间相互作用,并能够修饰受纳细胞中的生物过程。为了获取关于存在于血浆中 mRNA 分子来源的信息,我们使用 RNA 测序分析了健康个体的血浆细胞外 RNA(exRNA),并将其与同一个体的外周血单核细胞(PBMCs)进行了比较。结果数据表明,血浆中大部分转录本来自于除 PBMCs 以外的细胞类型。为了评估血浆 exRNA 组成与衰老相关的变化,进行了基因本体富集分析,结果显示衰老导致生物学过程的功能下降。此外,通过差异表达分析对血浆 RNA 水平进行了分析,揭示了 10 个与衰老相关变化显著的转录本。因此,似乎血浆 exRNA 并非完全来自 PBMCs。相反,其他细胞类型提供 RNA 来构成血浆 exRNA 区室。在测试的年轻和老年个体中均如此。此外,由于衰老,血浆的 RNA 含量发生了显著变化,影响了重要的生物学过程。

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