Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study

被引:58
作者
Zhu, Yong [1 ]
Hu, Hong-Liang [1 ]
Li, Peng [1 ]
Yang, Shi [1 ]
Zhang, Wei [1 ]
Ding, Hui [1 ]
Tian, Ru-Hui [1 ]
Ning, Ye [1 ]
Zhang, Ling-Ling [2 ]
Guo, Xi-Zhi [2 ]
Shi, Zhan-Ping [1 ]
Li, Zheng [1 ]
He, Zuping [3 ,4 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Human Sperm Bank, Shanghai Inst Androl, Renji Hosp,Sperm Dev & Genet Lab,Sch Med,Dept Uro, Shanghai 200001, Peoples R China
[2] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200240, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Clin Stem Cell Res Ctr, Shanghai 200127, Peoples R China
[4] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA
关键词
differentiation; induced pluripotent stem cells; male germ cells; retinoic acid; transplantation; RETINOIC ACID; MOUSE; DERIVATION; MICE;
D O I
10.1038/aja.2012.3
中图分类号
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
摘要
Recent studies have reported that induced pluripotent stem (iPS) cells from mice and humans can differentiate into primordial germ cells. However, whether iPS cells are capable of producing male germ cells is not known. The objective of this study was to investigate the differentiation potential of mouse iPS cells into spermatogonial stem cells and late-stage male germ cells. We used an approach that combines in vitro differentiation and in vivo transplantation. Embryoid bodies (EBs) were obtained from iPS cells using leukaemia inhibitor factor (LIF)-free medium. Quantitative PCR revealed a decrease in Oct4 expression and an increase in Stra8 and Vasa mRNA in the EBs derived from iPS cells. iPS cell-derived EBs were induced by retinoic acid to differentiate into spermatogonial stem cells (SSCs), as evidenced by their expression of VASA, as well as CDH1 and GFR alpha 1, which are markers of SSCs. Furthermore, these germ cells derived from iPS cells were transplanted into recipient testes of mice that had been pre-treated with busulfan. Notably, iPS cell-derived SSCs were able to differentiate into male germ cells ranging from spermatogonia to round spermatids, as shown by VASA and SCP3 expression. This study demonstrates that iPS cells have the potential to differentiate into late-stage male germ cells. The derivation of male germ cells from iPS cells has potential applications in the treatment of male infertility and provides a model for uncovering the molecular mechanisms underlying male germ cell development. Asian Journal of Andrology (2012) 14, 574-579; doi:10.1038/aja.2012.3; published online 16 April 2012
引用
收藏
页码:574 / 579
页数:6
相关论文
共 21 条
  • [1] In vitro post-meiotic germ cell development from human embryonic stem cells
    Aflatoonian, B.
    Ruban, L.
    Jones, M.
    Aflatoonian, R.
    Fazeli, A.
    Moore, H. D.
    [J]. HUMAN REPRODUCTION, 2009, 24 (12) : 3150 - 3159
  • [2] 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
  • [3] Retinoic acid, meiosis and germ cell fate in mammals
    Bowles, Josephine
    Koopman, Peter
    [J]. DEVELOPMENT, 2007, 134 (19): : 3401 - 3411
  • [4] Infertility in men: Recent advances and continuing controversies
    De Kretser, DM
    Baker, HWG
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1999, 84 (10) : 3443 - 3450
  • [5] 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
  • [6] Nodal Signaling via an Autocrine Pathway Promotes Proliferation of Mouse Spermatogonial Stem/Progenitor Cells Through Smad2/3 and Oct-4 Activation
    He, Zuping
    Jiang, Jiji
    Kokkinaki, Maria
    Dym, Martin
    [J]. STEM CELLS, 2009, 27 (10) : 2580 - 2590
  • [7] Derivation of oocytes from mouse embryonic stem cells
    Hübner, K
    Fuhrmann, G
    Christenson, LK
    Kehler, J
    Reinbold, R
    De La Fuente, R
    Wood, J
    Strauss, JF
    Boiani, M
    Schöler, HR
    [J]. SCIENCE, 2003, 300 (5623) : 1251 - 1256
  • [8] Induction of Primordial Germ Cells From Mouse Induced Pluripotent Stem Cells Derived From Adult Hepatocytes
    Imamura, Masanori
    Aoi, Takashi
    Tokumasu, Ako
    Mise, Nathan
    Abe, Kuniya
    Yamanaka, Shinya
    Noce, Toshiaki
    [J]. MOLECULAR REPRODUCTION AND DEVELOPMENT, 2010, 77 (09) : 802 - 811
  • [9] Retinoic acid regulates sex-specific timing of meiotic initiation in mice
    Koubova, J
    Menke, DB
    Zhou, Q
    Capel, B
    Griswold, MD
    Page, DC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (08) : 2474 - 2479
  • [10] Germline-Competent Mouse-Induced Pluripotent Stem Cell Lines Generated on Human Fibroblasts without Exogenous Leukemia Inhibitory Factor
    Li, Chunliang
    Yu, Hongyao
    Ma, Yu
    Shi, Guilai
    Jiang, Jing
    Gu, Junjie
    Yang, Ying
    Jin, Shibo
    Wei, Zhe
    Jiang, Hua
    Li, Jinsong
    Jin, Ying
    [J]. PLOS ONE, 2009, 4 (08):