Functional primordial germ cell-like cells from pluripotent stem cells in rats

被引:34
|
作者
Oikawa, Mami [1 ,2 ]
Kobayashi, Hisato [3 ]
Sanbo, Makoto [2 ]
Mizuno, Naoaki [4 ]
Iwatsuki, Kenyu [1 ,5 ]
Takashima, Tomoya [3 ,6 ]
Yamauchi, Keiko [2 ]
Yoshida, Fumika [2 ]
Yamamoto, Takuya [7 ,8 ,9 ]
Shinohara, Takashi [10 ]
Nakauchi, Hiromitsu [4 ,11 ]
Kurimoto, Kazuki [3 ]
Hirabayashi, Masumi [2 ,12 ]
Kobayashi, Toshihiro [1 ,2 ]
机构
[1] Univ Tokyo, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci, Div Mammalian Embryol,Minato Ku, Tokyo 1088639, Japan
[2] Natl Inst Physiol Sci, Ctr Genet Anal Behav, Okazaki, Aichi 4448787, Japan
[3] Nara Med Univ, Dept Embryol, Kashihara, Nara 6340813, Japan
[4] Univ Tokyo, Inst Med Sci, Div Stem Cell Therapy, Distinguished Prof Unit,Minato Ku, Tokyo 1088639, Japan
[5] Shinshu Univ, Grad Sch Med Sci & Technol, Ueda, Nagano 3868567, Japan
[6] Tokyo Univ Agr, Dept Biosci, Setagaya Ku, Tokyo 1568502, Japan
[7] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, Kyoto 6068507, Japan
[8] Kyoto Univ, Inst Adv Study Human Biol, Sakyo Ku, Kyoto 6068501, Japan
[9] RIKEN, Ctr Adv Intelligence Project, Med Risk Avoidance Based iPS Cells Team, Sakyo Ku, Kyoto 6068507, Japan
[10] Kyoto Univ, Grad Sch Med, Dept Mol Genet, Sakyo Ku, Kyoto 6068501, Japan
[11] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Dept Genet, Sch Med, Stanford, CA 94305 USA
[12] Grad Univ Adv Studies, Okazaki, Aichi 4448787, Japan
基金
日本学术振兴会; 芬兰科学院;
关键词
LINEAGE; COMPLEMENTATION; SPECIFICATION; GENERATION; SPERMATIDS; DNA;
D O I
10.1126/science.abl4412
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell-like cells (PGCLCs) to produce gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. When rat PGCLCs are transplanted into the seminiferous tubules of germline-less rats, functional spermatids-that is, those capable of siring viable offspring-are generated. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis.
引用
收藏
页码:176 / +
页数:40
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