Epigenetic reprogramming of the germ cell nuclear factor gene is required for proper differentiation of induced pluripotent cells.
Epigenetic reprogramming of the germ cell nuclear factor gene is required for proper differentiation of induced pluripotent cells.
复制标题
诱导多能细胞的正确分化需要生殖细胞核因子基因的表观遗传重编程。
DOI：
10.1002/stem.1367
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Cooney,AustinJ
中科院分区：
文献类型：
--
作者：
Wang,Hongran;Wang,Xiaohong;Xu,Xueping;Zwaka,ThomasP;Cooney,AustinJ
Somatic cells have been reprogrammed into induced pluripotent stem (iPS) cells that recapitulate the pluripotent nature of embryonic stem (ES) cells. Reduced pluripotency and variable differentiation capacities have hampered progress with this technology for applications in regeneration medicine. We have previously shown that germ cell nuclear factor (Gcnf) is required for the repression of pluripotency genes during ES cell differentiation and embryonic development. Here we report that iPS cell lines, in which theGcnfgene was properly reprogrammed, allowing expression ofGcnf, repress pluripotency genes during subsequent differentiation. In contrast, iPS clones in which theGcnfgene was not reprogrammed maintained pluripotency gene expression during differentiation and did not differentiate properly either in vivo or in vitro. These mal-reprogrammed cells recapitulated the phenotype ofGcnfknockout (Gcnf−/−) ES cells. Reintroduction ofGcnfinto either theGcnfnegative iPS cells or theGcnf−/−ES cells rescued repression ofOct4during differentiation. Our findings establish a key role forGcnfas a regulator of iPS cell pluripotency gene expression. It also demonstrates that reactivation of theGcnfgene may serve as a marker to distinguish completely reprogrammed iPS cells from incompletely pluripotent cells, which would make therapeutic use of iPS cells safer and more practical as it would reduce the oncogenic potential of iPS cells. STEMCells2013;31:2659–2666
