2012年10月9日 讯 /生物谷BIOON/ --在一项研究中，西班牙巴塞罗那市Bellvitge生物医学研究所癌症表观遗传学与生物学项目(Cancer Epigenetics and Biology Program at the Bellvitge Biomedical Research Institute, IDIBELL)主任Manel Esteller和同事们鉴定出成体干细胞产生人体不同组织时发生的表观遗传变化。相关研究结果于2012年10月1日在线刊登在American Journal of Pathology期刊上。
人体中每个细胞的基因组都是一样的。然而，组织和器官的活性以及它们的功能故障并不能够充分地通过基因组来加以解释。然而，表观遗传学能够解释其中一部分。最为常见的表观遗传标记是加入甲基基团到DNA之上。因此，表观基因组就是获得一个有机体中的所有表观遗传标记。
成体干细胞拥有很大的潜力来再生受损的器官，而且使用它们也能够避免利用胚胎干细胞时相关联的伦理问题，同时也可避免利用诱导性干细胞时产生的技术问题。在这项研究中，研究人员从身体脂肪中分离出干细胞，然后将它们转化为肌细胞和骨细胞。因此，他们必须知道在实验室中产生的这些细胞与一个人体内存在的拥有多少类似之处以及它们是否能够安全地被移植到病人体内。这项研究证实实验室细胞培养物的表观基因组与骨骼肌细胞中的非常相似，而且它们在本性上是自发存在的，不过它们并不是完全相同的。
这项研究的重点在于在实验室中产生的肌细胞和骨细胞跟来源自肿瘤组织(分别是横纹肌肉瘤和骨肉瘤)的肿瘤表观基因组并不相同，因此从生物学角度上来看，它们是安全的。Manel Esteller强调这项研究证实了利用表观遗传学可以确定用于再生医学来对抗不同疾病的已分化组织的成熟度和生物安全性。(生物谷Bioon.com)
doi: 10.1016/j.ajpath.2012.08.016
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DNA Methylation Plasticity of Human Adipose-Derived Stem Cells in Lineage Commitment
María Berdasco, Consolación Melguizo, Jose Prados, Antonio Gómez, Miguel Alaminos, Miguel A. Pujana, Miguel Lopez, Fernando Setien, Raul Ortiz, Inma Zafra, Antonia Aranega, Manel Esteller
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.
