2012年10月9日 訊 /生物谷BIOON/ --在一項(xiàng)研究中，西班牙巴塞羅那市Bellvitge生物醫(yī)學(xué)研究所癌癥表觀遺傳學(xué)與生物學(xué)項(xiàng)目(Cancer Epigenetics and Biology Program at the Bellvitge Biomedical Research Institute, IDIBELL)主任Manel Esteller和同事們鑒定出成體干細(xì)胞產(chǎn)生人體不同組織時(shí)發(fā)生的表觀遺傳變化,。相關(guān)研究結(jié)果于2012年10月1日在線刊登在American Journal of Pathology期刊上,。
人體中每個(gè)細(xì)胞的基因組都是一樣的。然而,，組織和器官的活性以及它們的功能故障并不能夠充分地通過(guò)基因組來(lái)加以解釋,。然而，表觀遺傳學(xué)能夠解釋其中一部分,。最為常見(jiàn)的表觀遺傳標(biāo)記是加入甲基基團(tuán)到DNA之上,。因此，表觀基因組就是獲得一個(gè)有機(jī)體中的所有表觀遺傳標(biāo)記,。
成體干細(xì)胞擁有很大的潛力來(lái)再生受損的器官,，而且使用它們也能夠避免利用胚胎干細(xì)胞時(shí)相關(guān)聯(lián)的倫理問(wèn)題，同時(shí)也可避免利用誘導(dǎo)性干細(xì)胞時(shí)產(chǎn)生的技術(shù)問(wèn)題,。在這項(xiàng)研究中,，研究人員從身體脂肪中分離出干細(xì)胞，然后將它們轉(zhuǎn)化為肌細(xì)胞和骨細(xì)胞,。因此,，他們必須知道在實(shí)驗(yàn)室中產(chǎn)生的這些細(xì)胞與一個(gè)人體內(nèi)存在的擁有多少類(lèi)似之處以及它們是否能夠安全地被移植到病人體內(nèi),。這項(xiàng)研究證實(shí)實(shí)驗(yàn)室細(xì)胞培養(yǎng)物的表觀基因組與骨骼肌細(xì)胞中的非常相似，而且它們?cè)诒拘陨鲜亲园l(fā)存在的,，不過(guò)它們并不是完全相同的,。
這項(xiàng)研究的重點(diǎn)在于在實(shí)驗(yàn)室中產(chǎn)生的肌細(xì)胞和骨細(xì)胞跟來(lái)源自腫瘤組織(分別是橫紋肌肉瘤和骨肉瘤)的腫瘤表觀基因組并不相同，因此從生物學(xué)角度上來(lái)看,，它們是安全的,。Manel Esteller強(qiáng)調(diào)這項(xiàng)研究證實(shí)了利用表觀遺傳學(xué)可以確定用于再生醫(yī)學(xué)來(lái)對(duì)抗不同疾病的已分化組織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.
