Genomic imprinting is variably lost during reprogramming of mouse iPS cells.
Genomic imprinting is variably lost during reprogramming of mouse iPS cells.
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DOI：
10.1016/j.scr.2013.05.011
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Li, Xiajun
中科院分区：
文献类型：
--
作者：
Takikawa, Sachiko;Ray, Chelsea;Wang, Xin;Shamis, Yulia;Wu, Tien-Yuan;Li, Xiajun
诱导多能干细胞（iPS）的衍生主要是表观遗传重编程过程。iPS细胞中基因组印记是如何重编程的，目前仍存在很大争议。因此，我们从遗传上相同的小鼠体细胞中获得了多个iPS克隆。我们发现，这些iPS克隆中的父母遗传印记是不完整的。与此同时，在相应的Snrpn和Peg3印迹区域的DNA甲基化印迹的损失，Snrpn和Zim1印迹基因的亲本来源特异性表达也失去了这些iPS克隆。iPS细胞中亲本基因组印记的这种损失可能是由iPS细胞衍生期间的重编程过程引起的，因为iPS细胞的延长培养不会导致基因组印记损失的显著增加。有趣的是，在高比例的iPS克隆中，一个到几个父系染色体似乎在Snrpn和Zac1印迹区域获得了从头甲基化。这些结果可能对iPS细胞未来的治疗应用具有一定的意义。由于DNA甲基化印记在某些iPS克隆中可以在多个印记区域被完全擦除，iPS细胞重编程也可以用于剖析哺乳动物基因组印记擦除、重新获得和维持的潜在机制。
Derivation of induced pluripotent stem (iPS) cells is mainly an epigenetic reprogramming process. It is still quite controversial how genomic imprinting is reprogrammed in iPS cells. Thus, we derived multiple iPS clones from genetically identical mouse somatic cells. We found that parentally inherited imprint was variably lost among these iPS clones. Concurrent with the loss of DNA methylation imprint at the corresponding Snrpn and Peg3 imprinted regions, parental origin-specific expression of the Snrpn and Zim1 imprinted genes was also lost in these iPS clones. This loss of parental genomic imprinting in iPS cells was likely caused by the reprogramming process during iPS cell derivation because extended culture of iPS cells did not lead to significant increase in the loss of genomic imprinting. Intriguingly, one to several paternal chromosomes appeared to have acquired de novo methylation at the Snrpn and Zac1 imprinted regions in a high percentage of iPS clones. These results might have some implications for future therapeutic applications of iPS cells. Since DNA methylation imprint can be completely erased in some iPS clones at multiple imprinted regions, iPS cell reprogramming may also be employed to dissect the underlying mechanisms of erasure, reacquisition and maintenance of genomic imprinting in mammals.
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影响因子：
15.9
作者：
Mabb, Angela M.;Judson, Matthew C.;Zylka, Mark J.;Philpot, Benjamin D.
通讯作者：
Philpot, Benjamin D.
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
--
作者：
Li, Xiajun;Leder, Philip
通讯作者：
Leder, Philip