近4年來(lái)國(guó)際干細(xì)胞研究熱點(diǎn)之一——誘導(dǎo)多能干細(xì)胞機(jī)理研究獲得突破性進(jìn)展：我國(guó)科學(xué)家的一項(xiàng)研究,，揭示了體細(xì)胞逆轉(zhuǎn)為多能干細(xì)胞的啟動(dòng)機(jī)制,，對(duì)誘導(dǎo)多能干細(xì)胞技術(shù)的完善與疾病治療具有指導(dǎo)意義,。
中國(guó)科學(xué)院廣州生物醫(yī)藥與健康研究院裴端卿研究員等人的這一研究成果，發(fā)表在北京時(shí)間18日出版的國(guó)際權(quán)威學(xué)術(shù)期刊《細(xì)胞·干細(xì)胞》上,。
該雜志同時(shí)發(fā)表了哈佛大學(xué)侯克林格博士的評(píng)論,，認(rèn)為這項(xiàng)工作揭示了間充質(zhì)—表皮細(xì)胞轉(zhuǎn)換過程在誘導(dǎo)多能干細(xì)胞形成中的關(guān)鍵作用，同時(shí)也顯示了細(xì)胞重編程,、發(fā)育的過程和癌變過程驚人相似,。
專家指出，這一發(fā)現(xiàn)不僅是誘導(dǎo)多能干細(xì)胞機(jī)理研究的突破性里程碑,，也為繼續(xù)改進(jìn)誘導(dǎo)多能干細(xì)胞技術(shù)提供了理論依據(jù),。
多能干細(xì)胞能夠定向分化為各種細(xì)胞、組織,、器官等,，也被稱為“萬(wàn)能細(xì)胞”。干細(xì)胞研究是近年來(lái)生命科學(xué)的熱點(diǎn)領(lǐng)域,，其在細(xì)胞治療,、組織器官移植和基因治療中具有重要意義；在新藥開發(fā)篩選與藥效,、新基因發(fā)掘與基因功能分析,、毒性評(píng)估等領(lǐng)域?qū)⒕哂兄匾挠绊憽?/p>
中科院廣州生物醫(yī)藥與健康研究院在國(guó)內(nèi)率先開展誘導(dǎo)多能干細(xì)胞研究。裴端卿研究員領(lǐng)導(dǎo)的研究團(tuán)隊(duì)近年來(lái)聚焦于多能干細(xì)胞的誘導(dǎo)機(jī)理和誘導(dǎo)效率兩個(gè)核心問題,，進(jìn)行了大量工作，取得了一系列成果,。
繼去年發(fā)現(xiàn)維生素C能加速誘導(dǎo)多能干細(xì)胞之后,，裴端卿團(tuán)隊(duì)的又一項(xiàng)研究成果揭示了形成誘導(dǎo)多能干細(xì)胞的重編程過程的啟動(dòng)機(jī)制。
相關(guān)閱讀：Cell Stem Cell：維生素C可提高iPS細(xì)胞誘導(dǎo)效率
“我們發(fā)現(xiàn)參與重編程的4個(gè)轉(zhuǎn)錄因子通過協(xié)同作用,，使實(shí)驗(yàn)中的成纖維細(xì)胞失去了原有的細(xì)胞特征,，‘變身’為具有表皮細(xì)胞特征的細(xì)胞，這一過程打開了通向多能干細(xì)胞的道路,。”裴端卿說(shuō),。（生物谷Bioon.net）
2010年干細(xì)胞技術(shù)與應(yīng)用講座
生物谷推薦原文出處：
Cell Stem Cell DOI:10.1016/j.stem.2010.04.014
A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts
Ronghui Li, Jialiang Liang, Su Ni, Ting Zhou, Xiaobing Qing, Huapeng Li, Wenzhi He, Jiekai Chen, Feng Li, Qiang Zhuang, Baoming Qin, Jianyong Xu, Wen Li, Jiayin Yang, Yi Gan, Dajiang Qin, Shipeng Feng, Hong Song, Dongshan Yang, Biliang Zhang, Lingwen Zeng, Liangxue Lai, Miguel Angel Esteban, Duanqing Pei
Epithelial-to-mesenchymal transition (EMT) is a developmental process important for cell fate determination. Fibroblasts, a product of EMT, can be reset into induced pluripotent stem cells (iPSCs) via exogenous transcription factors but the underlying mechanism is unclear. Here we show that the generation of iPSCs from mouse fibroblasts requires a mesenchymal-to-epithelial transition (MET) orchestrated by suppressing pro-EMT signals from the culture medium and activating an epithelial program inside the cells. At the transcriptional level, Sox2/Oct4 suppress the EMT mediator Snail, c-Myc downregulates TGF-β1 and TGF-β receptor 2, and Klf4 induces epithelial genes including E-cadherin. Blocking MET impairs the reprogramming of fibroblasts whereas preventing EMT in epithelial cells cultured with serum can produce iPSCs without Klf4 and c-Myc. Our work not only establishes MET as a key cellular mechanism toward induced pluripotency, but also demonstrates iPSC generation as a cooperative process between the defined factors and the extracellular milieu.
