近日,，國際權威細胞生物學雜志Journal of Cell Biology發(fā)表了健康所荊清課題組題為“Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells”的最新研究結果,。該研究揭示了染色質相關蛋白在渦蟲成體干細胞調控及再生過程中的重要作用及機制,。
淡水渦蟲(Planarian)被切割后，身體的一部分依然能再生出一個完整的渦蟲。其強大的再生能力依賴于體內豐富的成體干細胞（約占總細胞數(shù)目的25%）。渦蟲是最簡單的三胚層起源的生物，超過80%的基因與高等生物同源,，相關研究對于理解高等生物的干細胞調控，及神經,、肌肉,、生殖、腸道等系統(tǒng)的再生機理有重要意義,。近年來,，渦蟲基因組測序基本完成，RNAi篩選為基因功能研究提供了工具，但其再生中的表觀遺傳學調控機理并不清楚,。
研究組引進了國際通用的地中海渦蟲（Schmidtea mediterranea）單克隆品系,，發(fā)展并完善了渦蟲研究平臺，形成了一定的研究特色,。博士研究生曾安等結合RNAi篩選等技術,，系統(tǒng)地開展了成體干細胞介導再生過程中染色質調節(jié)機制的研究。通過克隆并篩選205個染色質相關蛋白,，研究人員發(fā)現(xiàn),，至少有12個染色質相關基因參與調節(jié)渦蟲再生過程。有趣的是,，渦蟲的HP1（Heterochromatin protein 1）同源基因HP1-1特異性地表達在渦蟲成體干細胞中,，對再生過程中新生芽基（Blastema）的長成是必需的。當HP1-1被敲低后,，干細胞自我更新受到抑制并導致其過早分化,。進一步研究發(fā)現(xiàn)在渦蟲受到損傷時，HP1-1與介導基因轉錄延伸(Transcription elongation)的FACT復合體互作,，上調增殖相關基因Mcm5的表達,，從而促進損傷后渦蟲成體干細胞的增殖反應，并起始再生過程中芽基形成,。通過研究組建立的渦蟲特異性抗體,、芯片及染色質免疫沉淀(ChIP)等實驗手段，揭示了表觀遺傳學調控渦蟲再生的機理,，并闡明了HP1-1調控干細胞行為的細胞及分子生物學基礎,，為深入研究表觀遺傳機制調控成體干細胞及再生提供了新的切入點。曾安同學因該研究而獲得2012年Keystone symposium干細胞年會授予的Future of Science Fund scholarship,。
該研究由國家自然科學基金、科技部重大科學研究計劃及中國科學院資助完成,。（生物谷Bioon.com）
doi:10.1083/jcb.201207172
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Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells
An Zeng, Yong-Qin Li, Chen Wang, Xiao-Shuai Han, Ge Li, Jian-Yong Wang, Dang-Sheng Li, Yong-Wen Qin, Yufang Shi, Gary Brewer, and Qing Jing
Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED–HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration.
