由于能使成體細(xì)胞“返老還童”為干細(xì)胞,，誘導(dǎo)多功能干細(xì)胞(iPS細(xì)胞)是近年來(lái)干細(xì)胞領(lǐng)域的研究熱點(diǎn),。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,、陳捷凱副研究員等人經(jīng)過(guò)多年努力，近日破解了iPS細(xì)胞誘導(dǎo)過(guò)程中一個(gè)極為重要的障礙，論文2日在線發(fā)表在《自然·遺傳學(xué)》雜志上。
研究過(guò)程中，裴端卿及其團(tuán)隊(duì)發(fā)現(xiàn)iPS細(xì)胞誘導(dǎo)過(guò)程中大量出現(xiàn)一類細(xì)胞克隆,，外觀,、生長(zhǎng)速度等各方面酷似干細(xì)胞，卻沒(méi)有干細(xì)胞應(yīng)有的基因表達(dá)和功能,。
經(jīng)過(guò)深入研究,，科學(xué)家發(fā)現(xiàn)誘導(dǎo)培養(yǎng)iPS細(xì)胞所使用的血清是誘發(fā)這個(gè)“路障”的元兇：細(xì)胞中的一種蛋白——BMP蛋白對(duì)重編程過(guò)程起抑制作用。
研究人員進(jìn)一步發(fā)現(xiàn),，這些酷似干細(xì)胞的“假貨”在某些誘導(dǎo)條件下,，如用維生素C處理，也會(huì)變成貨真價(jià)實(shí)的誘導(dǎo)多功能干細(xì)胞,。
哈佛大學(xué)再生醫(yī)學(xué)中心教授康拉德說(shuō),，這一發(fā)現(xiàn)是決定細(xì)胞命運(yùn)的分子機(jī)制研究的重大突破，將使研究者更高效更高質(zhì)量地制備誘導(dǎo)多功能干細(xì)胞,，加快制備來(lái)自病人疾病的特異細(xì)胞系,，加快阿爾茨海默氏癥、帕金森氏癥等疾病的藥物研發(fā),。（生物谷Bioon.com）
doi:10.1038/ng.2491
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H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs
Jiekai Chen, He Liu, Jing Liu, Jing Qi,， Bei Wei， Jiaqi Yang,， Hanquan Liang,， You Chen， Jing Chen,， Yaran Wu,， Lin Guo， Jieying Zhu,， Xiangjie Zhao,， Tianran Peng,， Yixin Zhang,， Shen Chen， Xuejia Li,， Dongwei Li,， Tao Wang， Duanqing Pei
The induction of pluripotent stem cells (iPSCs) by defined factors is poorly understood stepwise. Here, we show that histone H3 lysine 9 (H3K9) methylation is the primary epigenetic determinant for the intermediate pre-iPSC state, and its removal leads to fully reprogrammed iPSCs. We generated a panel of stable pre-iPSCs that exhibit pluripotent properties but do not activate the core pluripotency network, although they remain sensitive to vitamin C for conversion into iPSCs. Bone morphogenetic proteins (BMPs) were subsequently identified in serum as critical signaling molecules in arresting reprogramming at the pre-iPSC state. Mechanistically, we identified H3K9 methyltransferases as downstream targets of BMPs and showed that they function with their corresponding demethylases as the on/off switch for the pre-iPSC fate by regulating H3K9 methylation status at the core pluripotency loci. Our results not only establish pre-iPSCs as an epigenetically stable signpost along the reprogramming road map, but they also provide mechanistic insights into the epigenetic reprogramming of cell fate.
