Effects of Akt signaling on nuclear reprogramming

被引:19
作者
Nakamura, Toshinobu [1 ]
Inoue, Kimiko [3 ]
Ogawa, Shoko [2 ]
Umehara, Hiroki [1 ]
Ogonuki, Narumi [3 ]
Miki, Hiromi [3 ]
Kimura, Tohru [2 ]
Ogura, Atsuo [3 ]
Nakano, Toru [1 ,2 ]
机构
[1] Osaka Univ, Grad Sch Frontier Biosci, Osaka 8650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Pathol, Osaka 8650871, Japan
[3] RIKEN Bioresource Ctr, Tsukuba 3050074, Japan
关键词
D O I
10.1111/j.1365-2443.2008.01243.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Reprogramming of the epigenetic state from differentiated to pluripotent cells can be attained by cell fusion of differentiated somatic cells with embryonic stem (ES) cells or transfer of the nucleus of a differentiated cell into an enucleated oocyte. Activation of Akt signaling is sufficient to maintain pluripotency of ES cells and promotes derivation of embryonic germ (EG) cells from primordial germ cells (PGCs). Here we analyzed the effects of Akt signaling on somatic cell nuclear reprogramming after cell fusion and nuclear transfer. We found that forced activation of Akt signaling stimulated reprogramming after cell fusion of ES cells with thymocytes or mouse embryonic fibroblasts. These hybrid cells showed ES cell characteristics, including in vitro and in vivo differentiation capacity. In contrast, Akt signaling significantly reduced the efficiency of reprogramming with nuclear transfer. Our results demonstrate that Akt signaling plays important roles on the nuclear reprogramming of somatic cells.
引用
收藏
页码:1269 / 1277
页数:9
相关论文
共 40 条
[1]   Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes [J].
Baxter, J ;
Sauer, S ;
Peters, A ;
John, R ;
Williams, R ;
Caparros, ML ;
Arney, K ;
Otte, A ;
Jenuwein, T ;
Merkenschlager, M ;
Fisher, AG .
EMBO JOURNAL, 2004, 23 (22) :4462-4472
[2]   Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus [J].
Blelloch, Robert ;
Wang, Zhongde ;
Meissner, Alex ;
Pollard, Steven ;
Smith, Austin ;
Jaenisch, Rudolf .
STEM CELLS, 2006, 24 (09) :2007-2013
[3]   Advances in protein kinase B signalling:: AKTion on multiple fronts [J].
Brazil, DP ;
Yang, ZZ ;
Hemmings, BA .
TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (05) :233-242
[4]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[5]   Akt-mediated phsophorylationof EZH2 suppresses methylation of lysine 27 in histone H3 [J].
Cha, TL ;
Zhou, BHP ;
Xia, WY ;
Wu, YD ;
Yang, CC ;
Chen, CT ;
Ping, B ;
Otte, AP ;
Hung, MC .
SCIENCE, 2005, 310 (5746) :306-310
[6]   Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells [J].
Cowan, CA ;
Atienza, J ;
Melton, DA ;
Eggan, K .
SCIENCE, 2005, 309 (5739) :1369-1373
[7]   Nuclei of embryonic stem cells reprogram somatic cells [J].
Do, JT ;
Schöler, HR .
STEM CELLS, 2004, 22 (06) :941-949
[8]   Involvement of protein kinase B/AKT in early development of mouse fertilized eggs [J].
Feng, Chen ;
Yu, Aiming ;
Liu, Ying ;
Zhang, Jie ;
Zong, Zhihong ;
Su, Wenhui ;
Zhang, Zhe ;
Yu, Dahai ;
Sun, Qing-Yuan ;
Yu, Bingzhi .
BIOLOGY OF REPRODUCTION, 2007, 77 (03) :560-568
[9]   Nuclear reprogramming and pluripotency [J].
Hochedlinger, Konrad ;
Jaenisch, Rudolf .
NATURE, 2006, 441 (7097) :1061-1067
[10]   Akt-phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity [J].
Huang, WC ;
Chen, CC .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (15) :6592-6602