Oct4-Induced Pluripotency in Adult Neural Stem Cells

被引:790
作者
Kim, Jeong Beom [1 ]
Sebastiano, Vittorio [1 ]
Wu, Guangming [1 ]
Arauzo-Bravo, Marcos J. [1 ]
Sasse, Philipp [2 ]
Gentile, Luca [1 ]
Ko, Kinarm [1 ]
Ruau, David [3 ]
Ehrich, Mathias [4 ]
van den Boom, Dirk [4 ]
Meyer, Johann [5 ]
Huebner, Karin [1 ]
Bernemann, Christof [1 ]
Ortmeier, Claudia [1 ]
Zenke, Martin [3 ]
Fleischmann, Bernd K. [2 ]
Zaehres, Holm [1 ]
Schoeler, Hans R. [1 ]
机构
[1] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, NRW, Germany
[2] Univ Bonn, Inst Physiol 1, Life & Brain Ctr, D-53105 Bonn, NRW, Germany
[3] RWTH Aachen Univ Med Sch, Inst Biomed Engn, Dept Cell Biol, D-52074 Aachen, NRW, Germany
[4] SEQUENOM Inc, San Diego, CA 92121 USA
[5] Hannover Med Sch, Dept Expt Hematol, D-30625 Hannover, Germany
关键词
PRIMORDIAL GERM-CELLS; HUMAN FIBROBLASTS; SELF-RENEWAL; MOUSE; GENERATION; EXPRESSION; DERIVATION; INDUCTION; OCT4; MYC;
D O I
10.1016/j.cell.2009.01.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem cells (1F iPS) are similar to embryonic stem cells in vitro and in vivo. Not only can these cells can be efficiently differentiated into NSCs, cardiomyocytes, and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
引用
收藏
页码:411 / 419
页数:9
相关论文
共 42 条
  • [1] Generation of pluripotent stem cells from adult mouse liver and stomach cells
    Aoi, Takashi
    Yae, Kojiro
    Nakagawa, Masato
    Ichisaka, Tomoko
    Okita, Keisuke
    Takahashi, Kazutoshi
    Chiba, Tsutomu
    Yamanaka, Shinya
    [J]. SCIENCE, 2008, 321 (5889) : 699 - 702
  • [2] Regulatory networks in embryo-derived pluripotent stem cells
    Boiani, M
    Schöler, HR
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (11) : 872 - 884
  • [3] Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells
    Brambrink, Tobias
    Foreman, Ruth
    Welstead, G. Grant
    Lengner, Christopher J.
    Wernig, Marius
    Suh, Heikyung
    Jaenisch, Rudolf
    [J]. CELL STEM CELL, 2008, 2 (02) : 151 - 159
  • [4] LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal
    Capela, A
    Temple, S
    [J]. NEURON, 2002, 35 (05) : 865 - 875
  • [5] Niche-independent symmetrical self-renewal of a mammalian tissue stem cell
    Conti, L
    Pollard, SM
    Gorba, T
    Reitano, E
    Toselli, M
    Biella, G
    Sun, YR
    Sanzone, S
    Ying, QL
    Cattaneo, E
    Smith, A
    [J]. PLOS BIOLOGY, 2005, 3 (09): : 1594 - 1606
  • [6] Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2
    Danwei Huangfu
    Osafune, Kenji
    Maehr, Rene
    Guo, Wenjun
    Eijkelenboom, Astrid
    Chen, Shuibing
    Muhlestein, Whitney
    Melton, Douglas A.
    [J]. NATURE BIOTECHNOLOGY, 2008, 26 (11) : 1269 - 1275
  • [7] Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry
    Ehrich, M
    Nelson, MR
    Stanssens, P
    Zabeau, M
    Liloglou, T
    Xinarianos, G
    Cantor, CR
    Field, JK
    van den Boom, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (44) : 15785 - 15790
  • [8] Derivation of Neural Stem Cells from Mesenchymal Stem Cells: Evidence for a Bipotential Stem Cell Population
    Fu, Lijuan
    Zhu, Lunjian
    Huang, Yu
    Lee, Tsung D.
    Forman, Stephen J.
    Shih, Chu-Chih
    [J]. STEM CELLS AND DEVELOPMENT, 2008, 17 (06) : 1109 - 1121
  • [9] Derivation of embryonic germ cells and male gametes from embryonic stem cells
    Geijsen, N
    Horoschak, M
    Kim, K
    Gribnau, J
    Eggan, K
    Daley, GQ
    [J]. NATURE, 2004, 427 (6970) : 148 - 154
  • [10] Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells
    Hermann, A
    Gastl, R
    Liebau, S
    Popa, MO
    Fiedler, J
    Boehm, BO
    Maisel, M
    Lerche, H
    Schwarz, J
    Brenner, R
    Storch, A
    [J]. JOURNAL OF CELL SCIENCE, 2004, 117 (19) : 4411 - 4422