1月16日,，《分子細(xì)胞生物學(xué)雜志》（Journal of Molecular Cell Biology）在線發(fā)表了中科院上海生科院生化與細(xì)胞所朱學(xué)良研究組的研究論文：“Nanog suppresses cell migration by downregulating Thymosin β4 and Rnd3”,。該研究發(fā)現(xiàn)干細(xì)胞轉(zhuǎn)錄因子Nanog可通過下調(diào)下游基因Thymosin β4和Rnd3的表達(dá)來抑制細(xì)胞的遷移，提示Nanog等轉(zhuǎn)錄因子能夠在調(diào)控胚胎干細(xì)胞干性的同時(shí)影響細(xì)胞的遷移能力,。
細(xì)胞遷移對(duì)胚胎發(fā)育的組織、器官形成等有重要貢獻(xiàn),。干細(xì)胞需要在一些特定的轉(zhuǎn)錄因子的作用下才能維持其干性,，在細(xì)胞分化的過程中這些轉(zhuǎn)錄因子的表達(dá)會(huì)被抑制。細(xì)胞分化往往也會(huì)伴隨細(xì)胞遷移能力的變化,。但這種變化是因?yàn)榫S持干性的轉(zhuǎn)錄因子也參與調(diào)節(jié)細(xì)胞遷移,，還是僅僅因?yàn)榉只蠹?xì)胞的性質(zhì)發(fā)生了根本改變？
朱學(xué)良研究組的研究生周釔灼等發(fā)現(xiàn),，在普通培養(yǎng)細(xì)胞內(nèi)異位表達(dá)Nanog,、Oct4、Sox2等干細(xì)胞轉(zhuǎn)錄因子能夠顯著抑制細(xì)胞的遷移,。針對(duì)Nanog的進(jìn)一步研究發(fā)現(xiàn)它通過下調(diào)Thymosin β4 and Rnd3兩個(gè)蛋白來影響微絲骨架的排布和粘著斑的定位,，進(jìn)而抑制細(xì)胞的遷移。Thymosin β4和Rnd3在小鼠的胚胎干細(xì)胞分化過程中的表達(dá)量與Nanog負(fù)相關(guān),，而在具有多分化潛能的小鼠畸胎瘤P19細(xì)胞內(nèi)敲低Nanog的表達(dá)則能夠促進(jìn)細(xì)胞遷移,。由于已知Nanog的表達(dá)水平在斑馬魚的囊胚階段高，但在原腸運(yùn)動(dòng)后期急劇下降,，在體實(shí)驗(yàn)選取斑馬魚早期胚胎作為研究對(duì)象,，發(fā)現(xiàn)在斑馬魚胚胎中持續(xù)性表達(dá)Nanog會(huì)抑制原腸運(yùn)動(dòng)過程中的細(xì)胞遷移。這些研究結(jié)果提示Nanog等轉(zhuǎn)錄因子具有調(diào)節(jié)干性和遷移能力的雙重作用,，這種兩面性可能有助于細(xì)胞分化和遷移的協(xié)調(diào),。
該課題得到了國(guó)家科技部、國(guó)家自然科學(xué)基金委和中國(guó)科學(xué)院的資助,。（生物谷Bioon.com）
doi:10.1093/jmcb/mjt002
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Nanog suppresses cell migration by downregulating thymosin β4 and Rnd3.
Zhou Y, Li S, Huang Q, Xie L, Zhu X.
Nanog, Sox2, and Oct4 are key transcription factors critical for the pluripotency and self-renewal of embryonic stem cells. Their downregulations lead to differentiation, accompanied with changes in cell motility. Whether these factors impact cell motility directly, however, is not clear. Here we addressed this question by initially assessing their effect in non-stem cells. We found that ectopic expression of Nanog, Sox2, or Oct4 markedly inhibited ECV304 cell migration. Detailed examinations revealed that Nanog induced disorganizations of the actin cytoskeleton and peripheral localizations of focal adhesions. These effects required its DNA-binding domain and are thus transcription-dependent. Furthermore, thymosin β4 and Rnd3 were identified as its downstream targets. Their depletions in ECV304 cells by RNAi phenocopied the ectopic expression of Nanog in both cell motility and actin organization, whereas their ectopic expressions rescued the migration defect of Nanog overexpression. Both proteins were upregulated during mouse embryonic stem cell differentiation. Their levels in the pluripotent mouse P19 cells also increased upon Nanog ablation, coincident with an increase in cell motility. Moreover, persistent expression of Nanog in zebrafish embryos suppressed gastrulation and cell migration. These results indeed suggest a dual role of certain transcription factors in the orchestration of differentiation and motility
