Yang Fan, Ren Yahui, Li Huan, Wang Huayan
Department of Animal Biotechnology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
J Cell Physiol. 2018 Feb;233(2):1601-1611. doi: 10.1002/jcp.26063. Epub 2017 Jul 31.
The estrogen-related receptor b (ESRRB) is an orphan nuclear receptor and targets many genes involved in self-renewal and pluripotency. In mouse ES cells, overexpression of ESRRB can maintain LIF-independent self-renewal in the absence of Nanog. However, the fundamental features of porcine ESRRB remain elusive. In this study, we revealed the expression profiles of ESRRB in both porcine pluripotent stem cells and early stage embryos and dissected the functional domains of ESRRB protein to prove that ESRRB is a key transcription factor that enhanced porcine pluripotent gene activation. Addition of ESRRB into the cocktail of core pluripotent factors Oct4, Sox2, Klf4, and c-Myc (OSKM + E) could significantly enhance the reprograming efficiency and the formation of alkaline phosphatase positive colonies. Conversely, knockdown of ESRRB in piPSCs significantly reduced the expression level of pluripotent genes, minimized the alkaline phosphatase activity, and initiated the porcine induced pluripotent stem cell differentiation. Therefore, porcine ESRRB is a crucial transcription factor to improve the self-renewal of piPSCs.
雌激素相关受体β(ESRRB)是一种孤儿核受体,作用于许多参与自我更新和多能性的基因。在小鼠胚胎干细胞中,ESRRB的过表达可在没有Nanog的情况下维持不依赖白血病抑制因子(LIF)的自我更新。然而,猪ESRRB的基本特征仍不清楚。在本研究中,我们揭示了ESRRB在猪多能干细胞和早期胚胎中的表达谱,并剖析了ESRRB蛋白的功能结构域,以证明ESRRB是增强猪多能基因激活的关键转录因子。将ESRRB添加到核心多能因子Oct4、Sox2、Klf4和c-Myc的组合中(OSKM + E)可显著提高重编程效率和碱性磷酸酶阳性集落的形成。相反,在猪诱导多能干细胞(piPSCs)中敲低ESRRB可显著降低多能基因的表达水平,使碱性磷酸酶活性最小化,并启动猪诱导多能干细胞分化。因此,猪ESRRB是改善piPSCs自我更新的关键转录因子。