Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Biomedical Research Institute, Barcelona, Spain.
Am J Pathol. 2012 Dec;181(6):2079-93. doi: 10.1016/j.ajpath.2012.08.016. Epub 2012 Sep 29.
Adult stem cells have an enormous potential for clinical use in regenerative medicine that avoids many of the drawbacks characteristic of embryonic stem cells and induced pluripotent stem cells. In this context, easily obtainable human adipose-derived stem cells offer an interesting option for future strategies in regenerative medicine. However, little is known about their repertoire of differentiation capacities, how closely they resemble the target primary tissues, and the potential safety issues associated with their use. DNA methylation is one of the most widely recognized epigenetic factors involved in cellular identity, prompting us to consider how the analyses of 27,578 CpG sites in the genome of these cells under different conditions reflect their different natural history. We show that human adipose-derived stem cells generate myogenic and osteogenic lineages that share much of the DNA methylation landscape characteristic of primary myocytes and osteocytes. Most important, adult stem cells and in vitro-generated myocytes and osteocytes display a significantly different DNA methylome from that observed in transformed cells from these tissue types, such as rhabdomyosarcoma and osteosarcoma. These results suggest that the plasticity of the DNA methylation patterns plays an important role in lineage commitment of adult stem cells and that it could be used for clinical purposes as a biomarker of efficient and safely differentiated cells.
成体干细胞在再生医学中有巨大的临床应用潜力，可以避免胚胎干细胞和诱导多能干细胞的许多缺点。在这种情况下，容易获得的人脂肪来源干细胞为再生医学的未来策略提供了一个有趣的选择。然而，人们对它们的分化能力谱、与靶组织的相似程度以及与使用相关的潜在安全问题知之甚少。DNA 甲基化是参与细胞身份的最广泛认可的表观遗传因素之一，促使我们考虑这些细胞在不同条件下的 27578 个基因组 CpG 位点的分析如何反映它们不同的自然史。我们表明，人脂肪来源干细胞产生的成肌细胞和成骨细胞谱系与原代肌细胞和骨细胞的特征性 DNA 甲基化景观有很大的相似性。最重要的是，成年干细胞和体外生成的肌细胞和骨细胞的 DNA 甲基组与来自这些组织类型的转化细胞（如横纹肌肉瘤和骨肉瘤）观察到的有显著不同。这些结果表明，DNA 甲基化模式的可塑性在成体干细胞的谱系决定中起着重要作用，并且可以作为有效和安全分化细胞的生物标志物用于临床目的。
