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基于单细胞转录组学的老年和年轻小鼠胰岛 β 细胞的生理学差异研究。

Islet β-cells physiological difference study of old and young mice based on single-cell transcriptomics.

机构信息

Provincial Clinical College, Fujian Medical University, Fuzhou, China.

Fujian Provincial Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, China.

出版信息

J Diabetes Investig. 2021 Oct;12(10):1775-1783. doi: 10.1111/jdi.13579. Epub 2021 Jun 25.

Abstract

AIMS/INTRODUCTION: Body aging is a universal biological process. With aging, cells undergo a series of physiological changes. The main feature is cell proliferation decline, although the cells still have normal functions. Pancreatic β-cells are no exception. However, the physiological senescence of β-cells, and the resulting function and transcriptome changes have rarely attracted attention. The specific senescence phenotype of β-cells remains unknown.

MATERIALS AND METHODS

Pancreatic samples from three female C57BL/6 mice with aged 2.5 months (young) mice and 20 months (old) were digested to a single-cell suspension and analyzed, with 10× Genomics single-cell ribonucleic acid sequencing, β-cells were determined by biosynthesis analysis, and differences between old and young mice were identified.

RESULTS

A total of 47 differential genes with significant and statistical significance were screened in β-cells (fold change >1.5, P < 0.05). In old mice, 27 genes were upregulated and 20 genes were downregulated. Genes Mt1, Mt2, Pyy, Gcg and Pnlip, and mitochondrial genes mt-Nd1, mt-Nd3, mt-Co1, mt-Co2 and mt-Co3 were found to be involved in cellular senescence. Transcription factors Jund and Fos were important regulators of senescence.

CONCLUSIONS

An overall difference was found between the pancreatic β-cells of old and young mice. Transcription factors facilitate transitions between pancreatic β-cells. These findings are worthy of deep exploration, and provide new resources and directions for the research of pancreatic aging in mice.

摘要

目的/引言: 机体衰老属于一种普遍的生物学过程。随着年龄的增长,细胞会经历一系列的生理变化。主要特征是细胞增殖能力下降,尽管细胞仍具有正常功能。胰腺β细胞也不例外。然而,β细胞的生理衰老以及由此导致的功能和转录组变化很少受到关注。β细胞的具体衰老表型仍不清楚。

材料和方法

从三只 2.5 月龄(年轻)和 20 月龄(年老)的雌性 C57BL/6 小鼠的胰腺组织中消化得到单细胞悬液并进行分析,使用 10× Genomics 单细胞 RNA 测序,通过生物合成分析确定β细胞,并鉴定年老和年轻小鼠之间的差异。

结果

在β细胞中筛选出 47 个具有显著统计学意义的差异基因(fold change >1.5,P < 0.05)。在年老小鼠中,有 27 个基因上调,20 个基因下调。发现基因 Mt1、Mt2、Pyy、Gcg 和 Pnlip 以及线粒体基因 mt-Nd1、mt-Nd3、mt-Co1、mt-Co2 和 mt-Co3 参与细胞衰老。转录因子 Jund 和 Fos 是衰老的重要调控因子。

结论

在年老和年轻小鼠的胰腺β细胞之间发现了整体差异。转录因子促进了胰腺β细胞之间的转变。这些发现值得深入探索,为小鼠胰腺衰老的研究提供了新的资源和方向。

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