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供体年龄和细胞传代相关的 DNA 甲基化调控的转录和表达景观在脂肪间充质干细胞中。

Landscape of transcription and expression regulated by DNA methylation related to age of donor and cell passage in adipose-derived mesenchymal stem cells.

机构信息

Department of Breast and Thyroid Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.

Department of Burn and Plastic Surgery, Guiping People’s Hospital, Guigping 537200, Guangxi, China.

出版信息

Aging (Albany NY). 2020 Oct 31;12(21):21186-21201. doi: 10.18632/aging.103809.

Abstract

Adipose-derived mesenchymal stem cells (ADSCs) are pluripotent stromal cells that can differentiate into a variety of cell types, including skin cells. High-throughput sequencing was performed on cells of different ages and cell passage, obtaining their methylation, mRNA expression, and protein profile data. The stemness of each sample was then calculated using the TCGAbiolinks package in R. Co-expression modules were identified using WGCNA, and a crosstalk analysis was performed on the corresponding modules. The ClusterProfile package was used for the functional annotation of module genes. Finally, the regulatory network diagram was visualized using the Cytoscape software. First, a total of 16 modules were identified, where 3 modules were screened that were most relevant to the phenotype. 29 genes were screened in combination of the RNA seq, DNA methylation seq and protein iTRAQ. Finally, a comprehensive landscape comprised of RNA expression, DNA methylation and protein profiles of age relevant ADSCs was constructed. Overall, the different omics of ADSCs were comprehensively analyzed in order to reveal mechanisms pertaining to their growth and development. The effects of age, cell passage, and stemness on the therapeutic effect of ADSCs were explored. Additionally, a theoretical basis for selecting appropriate ADSC donors for regenerative medicine was provided.

摘要

脂肪间充质干细胞(ADSCs)是多能基质细胞,可分化为多种细胞类型,包括皮肤细胞。对不同年龄和细胞传代的细胞进行高通量测序,获得其甲基化、mRNA 表达和蛋白质谱数据。然后使用 R 中的 TCGAbiolinks 包计算每个样本的干性。使用 WGCNA 识别共表达模块,并对相应模块进行串扰分析。使用 ClusterProfile 包对模块基因进行功能注释。最后,使用 Cytoscape 软件可视化调控网络图。首先,总共鉴定出 16 个模块,其中筛选出与表型最相关的 3 个模块。结合 RNA seq、DNA 甲基化 seq 和蛋白质 iTRAQ 筛选出 29 个基因。最后,构建了一个包含年龄相关 ADSCs 的 RNA 表达、DNA 甲基化和蛋白质谱的综合图谱。总之,全面分析 ADSCs 的不同组学,以揭示与生长和发育相关的机制。探讨了年龄、细胞传代和干性对 ADSCs 治疗效果的影响。此外,为选择合适的 ADSC 供体进行再生医学提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3def/7695361/3bbde2a0cbaf/aging-12-103809-g001.jpg

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