Epigenetic memory gained by priming with osteogenic induction medium improves osteogenesis and other properties of mesenchymal stem cells.
Epigenetic memory gained by priming with osteogenic induction medium improves osteogenesis and other properties of mesenchymal stem cells.
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通过成骨诱导培养基引发获得的表观遗传记忆可改善间充质干细胞的成骨和其他特性
DOI：
10.1038/srep11056
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发表时间：
2015-06-08
影响因子：
4.6
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Rui Y;Xu L;Chen R;Zhang T;Lin S;Hou Y;Liu Y;Meng F;Liu Z;Ni M;Tsang KS;Yang F;Wang C;Chan HC;Jiang X;Li G
间充质干细胞(MSCs)是一种高度可塑性的细胞，能够在适当的条件下进行转分化或去分化。在本研究中，我们报道了在体外诱导成骨分化后，MSCs可以转化为原始干细胞群(去分化成骨MSCs)，其细胞存活率、集落形成、成骨能力、迁移能力以及Nanog、Oct4和Sox2表达增加。最重要的是，我们的结果显示，在体内异位成骨方面，脱氧骨基质干细胞比未经处理的骨髓间充质干细胞有很大的优势。此外，在体外，MSCs中的Nanog基因敲除可以逆转De-Os-MSCs的这些增强特性，表明Nanog在转录网络中发挥中心作用。此外，包括DNA甲基化和组蛋白修饰在内的表观遗传调控可能在调控去成骨分化过程中发挥重要作用。我们发现，在Nanog和Oct4基因启动子上，H3K4me3和H4ac等组蛋白标志物的甲基化和启动子活性都降低了。综上所述，我们的研究表明，通过成骨诱导介质诱导的De-Os-MSCs获得的表观遗传记忆有利于其沿成骨细胞谱系分化，提高了细胞的存活和迁移能力，这可能在提高其在哺乳动物中的再生能力方面具有应用潜力。
Mesenchymal stem cells (MSCs) are highly plastic cells that are able to transdifferentiate or dedifferentiate under appropriate conditions. In the present study, we reported here that afterin vitroinduction of osteogenic differentiation, MSCs could be reverted to a primitive stem cell population (dedifferentiated osteogenic MSCs, De-Os-MSCs) with improved cell survival, colony formation, osteogenic potential, migratory capacity and increased expression of Nanog, Oct4 and Sox2. Most importantly, our results showed great superiority of the De-Os-MSCs over untreated MSCs in ectopic bone formation in vivo. Furthermore, Nanog-knockdown in MSCs could reverse these enhanced properties in De-Os-MSCs in vitro, indicating a central role of Nanog in the transcriptional network. In addition, epigenetic regulations including DNA methylation and histone modifications may play important roles in regulating the de-osteogenic differentiation process. And we found decreased methylation and promoter accrual of activating histone marks, such as H3K4me3 and H4ac on both Nanog and Oct4 gene promoters. Taken together, our study demonstrated that epigenetic memory in De-Os-MSCs gained by priming with osteogenic induction medium favored their differentiation along osteoblastic lineage with improved cell survival and migratory abilities, which may have application potential in enhancing their regenerative capacity in mammals.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4
作者：
Liu, Tong Ming;Wu, Ying Nan;Lim, Bing
通讯作者：
Lim, Bing
影响因子：
5.2
作者：
Kohler, Erin E.;Baruah, Jugajyoti;Urao, Norifumi;Ushio-Fukai, Masuko;Fukai, Tohru;Chatterjee, Ishita;Wary, Kishore K.
通讯作者：
Wary, Kishore K.
具有改善治疗潜力的去分化重编程间充质干细胞
影响因子：
5.2
作者：
Liu, Yang;Jiang, Xiaohua;Chan, Hsiao Chang
通讯作者：
Chan, Hsiao Chang
DOI：
10.1126/science.1191078
发表时间：
2010-10-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bonasio R;Tu S;Reinberg D
通讯作者：
Reinberg D