Generation of Germline-Competent Rat Induced Pluripotent Stem Cells

被引：64

作者：

Hamanaka, Sanae ^{[1
,2
]}

Yamaguchi, Tomoyuki ^{[1
,2
]}

Kobayashi, Toshihiro ^{[1
,2
]}

Kato-Itoh, Megumi ^{[2
]}

Yamazaki, Satoshi ^{[2
]}

Sato, Hideyuki ^{[2
]}

Umino, Ayumi ^{[2
]}

Wakiyama, Yukiko ^{[2
]}

Arai, Mami ^{[2
]}

Sanbo, Makoto ^{[3
]}

Hirabayashi, Masumi ^{[3
,4
]}

Nakauchi, Hiromitsu ^{[1
,2
]}

机构：

[1] Japan Sci & Technol Agcy, Exploratory Res Adv Technol ERATO, Nakauchi Stem Cell & Organ Regenerat Project, Tokyo, Japan

[2] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Stem Cell Therapy, Tokyo, Japan

[3] Natl Inst Physiol Sci, Ctr Genet Anal Behav, Okazaki, Aichi 444, Japan

[4] Grad Univ Adv Studies, Sch Life Sci, Okazaki, Aichi, Japan

来源：

PLOS ONE | 2011年 / 6卷 / 07期

基金：

日本科学技术振兴机构;

关键词：

HUMAN FIBROBLASTS; DEFINED FACTORS; MOUSE; LINES; ESTABLISHMENT; BLASTOCYSTS; MODELS; NANOG; PIG;

D O I：

10.1371/journal.pone.0022008

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Recent progress in rat pluripotent stem cell technology has been remarkable. Particularly salient is the demonstration that embryonic stem cells (ESCs) in the rat (rESCs) can contribute to germline transmission, permitting generation of gene-modified rats as is now done using mouse ESCs (mESCs) or mouse induced pluripotent stem cells (iPSCs; miPSCs). However, determinations of whether rat iPSCs (riPSCs) can contribute to germ cells are not published. Here we report the germline competency of riPSCs. Methodology/Principal Findings: We generated riPSCs by transducing three mouse reprogramming factors (Oct3/4, Klf4, and Sox2) into rat somatic cells, followed by culture in the presence of exogenous rat leukemia inhibitory factor (rLIF) and small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. We found that, like rESCs, our riPSCs can contribute to germline transmission. Furthermore we found, by immunostaining of testis from mouse-rat interspecific chimeras with antibody against mouse vasa homolog, that riPSCs can contribute to embryonic development with chimera formation in mice (rat-mouse interspecific chimeras) and to interspecific germlines. Conclusions/Significance: Our data clearly demonstrate that using only three reprogramming factors (Oct3/4, Klf4, and Sox2) rat somatic cells can be reprogrammed into a ground state. Our generated riPSCs exhibited germline transmission in either rat-rat intraspecific or mouse-rat interspecific chimeras.

引用

页数：9

共 32 条

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