Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan, 528231, Guangdong, China.
Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
BMC Genom Data. 2021 Dec 18;22(1):56. doi: 10.1186/s12863-021-01016-8.
Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying regulation mechanisms of these cells remain largely unknown.
BMMSCs and UCMSCs were isolated from inbred Wuzhishan miniature pigs and the first global DNA methylation and gene expression profiles of porcine MSCs were generated. The osteogenic and adipogenic differentiation ability of porcine BMMSCs is greater than that of UCMSCs. A total of 1979 genes were differentially expressed and 587 genes were differentially methylated at promoter regions in these cells. Integrative analysis revealed that 102 genes displayed differences in both gene expression and promoter methylation. Gene ontology enrichment analysis showed that these genes were associated with cell differentiation, migration, and immunogenicity. Remarkably, skeletal system development-related genes were significantly hypomethylated and upregulated, whereas cell cycle genes were opposite in UCMSCs, implying that these cells have higher cell proliferative activity and lower differentiation potential than BMMSCs.
Our results indicate that DNA methylation plays an important role in regulating the differences in biological characteristics of BMMSCs and UCMSCs. Results of this study provide a molecular theoretical basis for the application of porcine MSCs in human medicine.
骨髓（BM）和脐带（UC）是间充质干细胞（MSCs）的主要来源。这两种 MSCs 在许多生物学特性上存在显著差异，但这些细胞的潜在调节机制在很大程度上仍不清楚。
从近交五指山小型猪中分离出 BMMSCs 和 UCMSCs，并生成了猪 MSCs 的第一个全基因组 DNA 甲基化和基因表达谱。猪 BMMSCs 的成骨和脂肪生成分化能力大于 UCMSCs。这些细胞中共有 1979 个基因表达差异，587 个基因启动子区甲基化差异。综合分析显示，有 102 个基因在基因表达和启动子甲基化水平上均存在差异。基因本体论富集分析表明，这些基因与细胞分化、迁移和免疫原性有关。值得注意的是，与骨骼系统发育相关的基因在 UCMSCs 中呈现明显的低甲基化和上调，而细胞周期基因则相反，这表明这些细胞具有更高的细胞增殖活性和更低的分化潜能。
我们的研究结果表明，DNA 甲基化在调节 BMMSCs 和 UCMSCs 生物学特性差异方面发挥着重要作用。本研究结果为猪 MSCs 在人类医学中的应用提供了分子理论基础。
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