Abstract
BackgroundBone 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.ResultsBMMSCs 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.ConclusionsOur 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.
Highlights
Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs)
All animal procedures were approved by the Animal Care and Use Committee of Foshan University and all experiments were performed in accordance with the approved guidelines and regulations
UCMSCs were isolated from the umbilical cords of four Wuzhishan pig (WZSP) littermates on the day of birth, and BMMSCs were isolated from the bone marrow of the same individuals at 42 days after birth
Summary
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. The inbred WZSP line of pigs shows high genetic stability [14], and its inbreeding coefficient reached 0.994 at the 24th generation in 2013 [15]. This line has been widely used to study human diseases, including atherosclerosis, cardiovascular disease, xenotransplantation, and diabetes [16, 17].
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