Document Detail

Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study.
MedLine Citation:
PMID:  22504877     Owner:  NLM     Status:  MEDLINE    
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 GFRα1, 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.
Yong Zhu; Hong-Liang Hu; Peng Li; Shi Yang; Wei Zhang; Hui Ding; Ru-Hui Tian; Ye Ning; Ling-Ling Zhang; Xi-Zhi Guo; Zhan-Ping Shi; Zheng Li; Zuping He
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-16
Journal Detail:
Title:  Asian journal of andrology     Volume:  14     ISSN:  1745-7262     ISO Abbreviation:  Asian J. Androl.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-12-21     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  100942132     Medline TA:  Asian J Androl     Country:  China    
Other Details:
Languages:  eng     Pagination:  574-9     Citation Subset:  IM    
Renji Hospital, Sperm Development and Genetics Laboratory, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Department of Urology, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.
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MeSH Terms
Busulfan / pharmacology
Cell Cycle Proteins / metabolism
Cell Differentiation*
Cells, Cultured
DEAD-box RNA Helicases / metabolism
Embryoid Bodies / metabolism
Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
Induced Pluripotent Stem Cells / cytology*,  drug effects,  metabolism
Mice, Inbred C57BL
Nuclear Proteins / metabolism
Octamer Transcription Factor-3 / metabolism
Proteins / metabolism
RNA, Messenger / metabolism
Seminiferous Tubules / cytology*,  drug effects,  metabolism
Spermatogonia / cytology*,  transplantation
Spermatozoa / cytology*
Testis / metabolism
Tretinoin / pharmacology
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Fzr1 protein, mouse; 0/Gfra1 protein, mouse; 0/Glial Cell Line-Derived Neurotrophic Factor Receptors; 0/Nuclear Proteins; 0/Octamer Transcription Factor-3; 0/Pou5f1 protein, mouse; 0/Proteins; 0/RNA, Messenger; 0/Stra8 protein, mouse; 0/Sycp3 protein, mouse; 302-79-4/Tretinoin; 55-98-1/Busulfan; EC 3.6.1.-/DEAD-box RNA Helicases; EC 3.6.1.-/Ddx4 protein, mouse

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