Nanog Is Dispensable for the Generation of Induced Pluripotent Stem Cells

作者: Benjamin A. Schwarz , Ori Bar-Nur , José C.R. Silva , Konrad Hochedlinger

DOI: 10.1016/J.CUB.2013.12.050

关键词:

摘要: Summary Cellular reprogramming from somatic cells to induced pluripotent stem (iPSCs) can be achieved through forced expression of the transcription factors Oct4 , Klf4 Sox2 and c-Myc ( OKSM ) [1–4]. These factors, in combination with environmental cues, induce a stable intrinsic pluripotency network that confers indefinite self-renewal capacity on iPSCs. In addition homeodomain-containing factor Nanog is an integral part [5–11]. Although not required for maintenance cells, it has been reported essential establishment both embryonic (ESCs) blastocysts iPSCs [10, 12]. Here we revisit role direct reprogramming. Surprisingly, find dispensable iPSC formation under optimized culture conditions. We further document -deficient are transcriptionally highly similar wild-type support generation teratomas chimeric mice. Lastly, provide evidence presence ascorbic acid media critical overcoming previously observed block knockout cells.

参考文章(25)
Jonghwan Kim, Jianlin Chu, Xiaohua Shen, Jianlong Wang, Stuart H. Orkin, An extended transcriptional network for pluripotency of embryonic stem cells Cell. ,vol. 132, pp. 1049- 1061 ,(2008) , 10.1016/J.CELL.2008.02.039
Xi Chen, Han Xu, Ping Yuan, Fang Fang, Mikael Huss, Vinsensius B. Vega, Eleanor Wong, Yuriy L. Orlov, Weiwei Zhang, Jianming Jiang, Yuin-Han Loh, Hock Chuan Yeo, Zhen Xuan Yeo, Vipin Narang, Kunde Ramamoorthy Govindarajan, Bernard Leong, Atif Shahab, Yijun Ruan, Guillaume Bourque, Wing-Kin Sung, Neil D. Clarke, Chia-Lin Wei, Huck-Hui Ng, Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells Cell. ,vol. 133, pp. 1106- 1117 ,(2008) , 10.1016/J.CELL.2008.04.043
Matthias Stadtfeld, Effie Apostolou, Hidenori Akutsu, Atsushi Fukuda, Patricia Follett, Sridaran Natesan, Tomohiro Kono, Toshi Shioda, Konrad Hochedlinger, Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells Nature. ,vol. 465, pp. 175- 181 ,(2010) , 10.1038/NATURE09017
Miguel Ramalho-Santos, Soonsang Yoon, Yumi Matsuzaki, Richard C Mulligan, Douglas A Melton, "Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells Science. ,vol. 298, pp. 597- 600 ,(2002) , 10.1126/SCIENCE.1072530
Marius Wernig, Alexander Meissner, Ruth Foreman, Tobias Brambrink, Manching Ku, Konrad Hochedlinger, Bradley E. Bernstein, Rudolf Jaenisch, In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state Nature. ,vol. 448, pp. 318- 324 ,(2007) , 10.1038/NATURE05944
Kathryn Blaschke, Kevin T. Ebata, Mohammad M. Karimi, Jorge A. Zepeda-Martínez, Preeti Goyal, Sahasransu Mahapatra, Angela Tam, Diana J. Laird, Martin Hirst, Anjana Rao, Matthew C. Lorincz, Miguel Ramalho-Santos, Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells Nature. ,vol. 500, pp. 222- 226 ,(2013) , 10.1038/NATURE12362
Tobias Brambrink, Ruth Foreman, G. Grant Welstead, Christopher J. Lengner, Marius Wernig, Heikyung Suh, Rudolf Jaenisch, Sequential Expression of Pluripotency Markers during Direct Reprogramming of Mouse Somatic Cells Cell Stem Cell. ,vol. 2, pp. 151- 159 ,(2008) , 10.1016/J.STEM.2008.01.004
Cesar A. Sommer, Matthias Stadtfeld, George J. Murphy, Konrad Hochedlinger, Darrell N. Kotton, Gustavo Mostoslavsky, Induced Pluripotent Stem Cell Generation Using a Single Lentiviral Stem Cell Cassette Stem Cells. ,vol. 27, pp. 543- 549 ,(2009) , 10.1634/STEMCELLS.2008-1075
Nimet Maherali, Rupa Sridharan, Wei Xie, Jochen Utikal, Sarah Eminli, Katrin Arnold, Matthias Stadtfeld, Robin Yachechko, Jason Tchieu, Rudolf Jaenisch, Kathrin Plath, Konrad Hochedlinger, None, Directly Reprogrammed Fibroblasts Show Global Epigenetic Remodeling and Widespread Tissue Contribution Cell Stem Cell. ,vol. 1, pp. 55- 70 ,(2007) , 10.1016/J.STEM.2007.05.014
Yael Costa, Junjun Ding, Thorold W. Theunissen, Francesco Faiola, Timothy A. Hore, Pavel V. Shliaha, Miguel Fidalgo, Arven Saunders, Moyra Lawrence, Sabine Dietmann, Satyabrata Das, Dana N. Levasseur, Zhe Li, Mingjiang Xu, Wolf Reik, José C. R. Silva, Jianlong Wang, NANOG-dependent function of TET1 and TET2 in establishment of pluripotency Nature. ,vol. 495, pp. 370- 374 ,(2013) , 10.1038/NATURE11925