Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres.
Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres.
复制标题
DOI：
10.1016/j.celrep.2013.02.012
复制
发表时间：
2013-03-28
期刊：
影响因子：
8.8
通讯作者：
Puri PL
中科院分区：
文献类型：
--
作者：
Albini S;Coutinho P;Malecova B;Giordani L;Savchenko A;Forcales SV;Puri PL
从人类胚胎干细胞(HESCs)直接培养成肌细胞并形成三维收缩结构用于盘中疾病建模是当前再生医学中的一个挑战。以前的研究报道了从胚胎干细胞衍生的类胚体(EB)中产生成肌细胞，但不能从未分化的胚胎干细胞中产生成肌细胞，这表明需要中胚层的转变来促进骨骼肌的发生。在这里，我们发现选择性缺失SWI/SNF组分BAF60c(由SMARCD3编码)使hESCs对MyoD介导的骨骼肌生成的激活具有抵抗力。BAF60c的强制表达使MyoD能够通过指导MyoD核定位和允许靶基因染色质重塑来直接激活hESCs中的骨骼肌生成。表达BAF60c/MyoD的hESCs是表观遗传的肌源性祖细胞，它们绕过了中胚层的要求，当以浮动簇的形式培养时，可以产生由骨骼肌管组成的收缩的三维肌球。这些结果确定BAF60c是hESC致力于肌源性谱系的关键表观遗传决定因素，并为史无前例的hESC来源肌球的产生奠定了分子基础，这些肌球可用于肌肉疾病的“in DISH模型”。
Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs) and formation of tri-dimensional contractile structures for in dish disease modeling is a current challenge in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB), but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3) confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs, by instructing MyoD nuclear positioning and allowing chromatin remodelling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile tri-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as key epigenetic determinant of hESC commitment to the myogenic lineage, and establish the molecular basis for the unprecedented generation of hESC-derived myospheres exploitable for “in dish models” of muscular diseases.
登录
查看更多内容
影响因子：
3.7
作者：
Krauss RS
通讯作者：
Krauss RS
影响因子：
11.4
作者：
Reyes, JC;Barra, J;Yaniv, M
通讯作者：
Yaniv, M
影响因子：
11.4
作者：
Ohkawa, Y;Marfella, CGA;Imbalzano, AN
通讯作者：
Imbalzano, AN
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
5.2
作者：
Iacovino, Michelina;Bosnakovski, Darko;Fey, Holger;Rux, Danielle;Bajwa, Gagan;Mahen, Elisabeth;Mitanoska, Ana;Xu, Zhaohui;Kyba, Michael
通讯作者：
Kyba, Michael