Characterization and comparative DNA methylation profiling of four adipogenic genes in adipose-derived stem cells and de
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RESEARCH ARTICLE
Characterization and comparative DNA methylation profiling of four adipogenic genes in adipose‑derived stem cells and dedifferentiated fat cells from aging subjects Kallapat Tansriratanawong1 · Isao Tabei2 · Hiroshi Ishikawa3 · Akihiro Ohyama3 · Junko Toyomura3 · Soh Sato4 Received: 20 December 2019 / Accepted: 14 May 2020 © The Author(s) 2020
Abstract Adipose-derived stem cells (ASCs) and dedifferentiated fat (DFAT) cells are alternative cell sources in tissue engineering and regeneration because they are easily obtained and exhibit multilineage differentiation. However, aging may attenuate their regenerative potential and metabolic functions. Reports characterizing DFAT cells derived from aging donors are rare, and comparisons of DNA methylation profiles between aging ASCs and DFAT cells are poorly understood. Therefore, this study aimed to characterize DFAT cells relative to ASCs derived from aging subjects and compare the DNA methylation profiles of four adipogenic genes in these cells. ASCs and DFAT cells from aging donors exhibited characteristics similar to those of stem cells, including colony formation, proliferation, and multilineage differentiation abilities. However, compared with ASCs, DFAT cells exhibited increased proliferation, smooth muscle actin alpha (SMA-α) expression and decreased cellular senescence. DNA methylation profiling of ASCs and DFAT cells by combined bisulfite restriction analysis (COBRA) demonstrated hypermethylation patterns in three potent adipogenic genes—peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 4 (FABP4), and lipoprotein lipase (LPL)—but hypomethylation of CCAAT/enhancer binding protein alpha (C/EBPα) in the aging group. Statistically significant differences were observed between the aging group and the young group. Epigenetic regulation maintains the stability of ASCs and DFAT cells in an age-dependent manner. Our findings suggested that although the DNA methylation patterns of three adipogenic genes correlated with hypermethylation and aging, ASCs and DFAT cells exhibited cellular stability and several stem cell characteristics, offering further opportunities for personalized regeneration and energy maintenance by adipogenesis during aging. Keywords Adipose derived stem cells · DFAT cells · DNA methylation · Aging · Characterization · Epigenetics
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00379-x) contains supplementary material, which is available to authorized users. * Kallapat Tansriratanawong [email protected] 1
Department of Oral Medicine and Periodontology, Faculty of Dentistry, Mahidol University, 6 Yothi Street Rajthevi, Bangkok 10400, Thailand
2
Department of Surgery, Jikei University School of Medicine, Tokyo 105‑0003, Japan
3
Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305‑8575, Japan
4
Department of Periodontology, Nippon Dental University, Niigata 951‑1500, Japan
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