Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-02 DOI:10.1080/15592294.2024.2375011
Shuaichen Li, Puntita Siengdee, Frieder Hadlich, Nares Trakooljul, Michael Oster, Henry Reyer, Klaus Wimmers, Siriluck Ponsuksili
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引用次数: 0

Abstract

Mesenchymal stem cells (MSCs), with the ability to differentiate into osteoblasts, adipocytes, or chondrocytes, show evidence that the donor cell's metabolic type influences the osteogenic process. Limited knowledge exists on DNA methylation changes during osteogenic differentiation and the impact of diverse donor genetic backgrounds on MSC differentiation. In this study, synovial membrane mesenchymal stem cells (SMSCs) from two pig breeds (Angeln Saddleback, AS; German Landrace, DL) with distinct metabolic phenotypes were isolated, and the methylation pattern of SMSCs during osteogenic induction was investigated. Results showed that most differentially methylated regions (DMRs) were hypomethylated in osteogenic-induced SMSC group. These DMRs were enriched with genes of different osteogenic signalling pathways at different time points including Wnt, ECM, TGFB and BMP signalling pathways. AS pigs consistently exhibited a higher number of hypermethylated DMRs than DL pigs, particularly during the peak of osteogenesis (day 21). Predicting transcription factor motifs in regions of DMRs linked to osteogenic processes and donor breeds revealed influential motifs, including KLF1, NFATC3, ZNF148, ASCL1, FOXI1, and KLF5. These findings contribute to understanding the pattern of methylation changes promoting osteogenic differentiation, emphasizing the substantial role of donor the metabolic type and epigenetic memory of different donors on SMSC differentiation.

来自两个代谢不同品种的猪滑膜间充质干细胞成骨分化过程中 DNA 甲基化的动态变化。
间充质干细胞(MSCs)具有分化成成骨细胞、脂肪细胞或软骨细胞的能力,有证据表明供体细胞的代谢类型会影响成骨过程。关于成骨分化过程中 DNA 甲基化的变化以及不同供体遗传背景对间叶干细胞分化的影响,目前所知有限。本研究分离了两个代谢表型不同的猪种(Angeln Saddleback,AS;German Landrace,DL)的滑膜间充质干细胞(SMSCs),并研究了SMSCs在成骨诱导过程中的甲基化模式。结果表明,在成骨诱导的 SMSC 组中,大多数差异甲基化区域(DMR)都发生了低甲基化。这些DMRs富集了不同时间点不同成骨信号通路的基因,包括Wnt、ECM、TGFB和BMP信号通路。AS猪比DL猪表现出更多的高甲基化DMR,尤其是在成骨高峰期(第21天)。通过预测与成骨过程和供体品种相关的DMRs区域中的转录因子基团,发现了一些有影响的基团,包括KLF1、NFATC3、ZNF148、ASCL1、FOXI1和KLF5。这些发现有助于理解促进成骨分化的甲基化变化模式,强调了供体的代谢类型和不同供体的表观遗传记忆对SMSC分化的重要作用。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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