1月16日，《分子细胞生物学杂志》（Journal of Molecular Cell Biology）在线发表了中科院上海生科院生化与细胞所朱学良研究组的研究论文：“Nanog suppresses cell migration by downregulating Thymosin β4 and Rnd3”。该研究发现干细胞转录因子Nanog可通过下调下游基因Thymosin β4和Rnd3的表达来抑制细胞的迁移，提示Nanog等转录因子能够在调控胚胎干细胞干性的同时影响细胞的迁移能力。
细胞迁移对胚胎发育的组织、器官形成等有重要贡献。干细胞需要在一些特定的转录因子的作用下才能维持其干性，在细胞分化的过程中这些转录因子的表达会被抑制。细胞分化往往也会伴随细胞迁移能力的变化。但这种变化是因为维持干性的转录因子也参与调节细胞迁移，还是仅仅因为分化后细胞的性质发生了根本改变？
朱学良研究组的研究生周钇灼等发现，在普通培养细胞内异位表达Nanog、Oct4、Sox2等干细胞转录因子能够显著抑制细胞的迁移。针对Nanog的进一步研究发现它通过下调Thymosin β4 and Rnd3两个蛋白来影响微丝骨架的排布和粘着斑的定位，进而抑制细胞的迁移。Thymosin β4和Rnd3在小鼠的胚胎干细胞分化过程中的表达量与Nanog负相关，而在具有多分化潜能的小鼠畸胎瘤P19细胞内敲低Nanog的表达则能够促进细胞迁移。由于已知Nanog的表达水平在斑马鱼的囊胚阶段高，但在原肠运动后期急剧下降，在体实验选取斑马鱼早期胚胎作为研究对象，发现在斑马鱼胚胎中持续性表达Nanog会抑制原肠运动过程中的细胞迁移。这些研究结果提示Nanog等转录因子具有调节干性和迁移能力的双重作用，这种两面性可能有助于细胞分化和迁移的协调。
该课题得到了国家科技部、国家自然科学基金委和中国科学院的资助。（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
