Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency.
Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency.
复制标题
叉头盒家族转录因子作为细胞重编程多能性的多功能调节剂
DOI：
10.1186/s13619-021-00078-4
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发表时间：
2021-07-02
期刊：
影响因子：
--
通讯作者：
Pei D
中科院分区：
文献类型：
--
作者：
Fu M;Chen H;Cai Z;Yang Y;Feng Z;Zeng M;Chen L;Qin Y;Cai B;Zhu P;Zhou C;Yu S;Guo J;Liu J;Cao S;Pei D
叉头盒(Forkhead box，FOX)转录因子在哺乳动物发育和疾病中发挥重要作用。然而，它们在小鼠体细胞重编程中的作用尚不清楚。在此，我们报道了FOXD亚家族和FoxG1促进小鼠成纤维细胞诱导的多能干细胞(IPSCs)的产生，而FoxA和FoxO亚家族则明显地阻碍了这一过程。更重要的是，FoxD3、FoxD4和FoxG1可以分别取代Oct4，并与Sox2和Klf4一起产生具有胚系传播的IPSCs。相反，FoxO6通过抑制细胞增殖、抑制多能基因的表达、阻碍间充质向上皮细胞转化(MET)的过程，几乎完全阻断重编程。因此，我们的研究揭示了Fox转录因子在重编程中意想不到的作用，并为细胞命运转变提供了新的见解。网上版载有补充材料，可在10.1186/s13619-021-00078-4查阅。
Forkhead box (Fox) transcription factors play important roles in mammalian development and disease. However, their function in mouse somatic cell reprogramming remains unclear. Here, we report that FoxD subfamily and FoxG1 accelerate induced pluripotent stem cells (iPSCs) generation from mouse fibroblasts as early as day4 while FoxA and FoxO subfamily impede this process obviously. More importantly, FoxD3, FoxD4 and FoxG1 can replace Oct4 respectively and generate iPSCs with germline transmission together with Sox2 and Klf4. On the contrary, FoxO6 almost totally blocks reprogramming through inhibiting cell proliferation, suppressing the expression of pluripotent genes and hindering the process of mesenchymal to epithelial transition (MET). Thus, our study uncovers unexpected roles of Fox transcription factors in reprogramming and offers new insights into cell fate transition. The online version contains supplementary material available at 10.1186/s13619-021-00078-4.