Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.
Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.
复制标题
DOI：
10.1038/ng.1110
复制
发表时间：
2012-03-04
期刊：
影响因子：
30.8
通讯作者：
Hochedlinger, Konrad
中科院分区：
文献类型：
--
作者：
Stadtfeld, Matthias;Apostolou, Effie;Ferrari, Francesco;Choi, Jiho;Walsh, Ryan M.;Chen, Taiping;Ooi, Steen S. K.;Kim, Sang Yong;Bestor, Timothy H.;Shioda, Toshi;Park, Peter J.;Hochedlinger, Konrad
The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises the cells’ ability to generate entirely iPSC-derived adult mice (“all-iPSC mice”). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This allowed us to generate all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal animals. Our data demonstrate that transcription factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs.
登录
查看更多内容
影响因子：
64.5
作者：
Hanna, Jacob;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
3.5
作者：
Kato, Yuzuru;Kaneda, Masahiro;Sasaki, Hiroyuki
通讯作者：
Sasaki, Hiroyuki
影响因子：
23.9
作者：
Stadtfeld, Matthias;Maherali, Nimet;Hochedlinger, Konrad
通讯作者：
Hochedlinger, Konrad
DOI：
10.1073/pnas.2235866100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Coser, KR;Chesnes, J;Shioda, T
通讯作者：
Shioda, T
影响因子：
23.9
作者：
Carey, Bryce W.;Markoulaki, Styliani;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf