Li Rongyang, Tang Xiaochuan, Xu Shiyong, Chen Qing, Chen Baobao, Liu Shuo, Li Bojiang, Li Weijian, Yao Yilong, Wu Wangjun, Liu Honglin
College of Animal Sciences and Technology, Nanjing Agricultural University, Nanjing, China.
College of Animal Sciences and Technology, Guang Xi University, Nanning, China.
Reprod Domest Anim. 2018 Oct;53(5):1052-1059. doi: 10.1111/rda.13202. Epub 2018 Jul 20.
Small molecules discovered during the recent years can be used to regulate the growth of embryonic stem cells (ES cells). Chicken blastodermal cells (cBCs) play an important role in both basic and transgenic researches as an important ES cell. However, the regulatory mechanism of small molecules involved in the self-renewal and pluripotency of cBCs remains unknown. This study revealed that the small molecule, SC1, can maintain cBCs in an undifferentiated, pluripotent state in serum- and feeder-free E8 media without leukaemia inhibitory factor. Furthermore, SC1 inhibits downregulation of pluripotency-related genes caused by retinoic acid and promotes the proliferation of cBCs. Furthermore, the results of this study indicated that SC1 functions by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation, thus promoting the expression of pluripotency-related genes and maintaining the pluripotency of cBCs. The results also demonstrated that SC1 sustains the self-renewal capacity and pluripotency of cBCs cells by inhibiting ERK1 phosphorylation and promoting Akt phosphorylation. This kind of regulatory mechanism might be conserved in avian ES cells. Other molecules, similar to SC1, might provide insights into the molecular mechanisms that control the fate of stem cells and ultimately help in-vivo stem cell biology and therapy.
近年来发现的小分子可用于调控胚胎干细胞(ES细胞)的生长。鸡胚盘细胞(cBCs)作为一种重要的ES细胞,在基础研究和转基因研究中都发挥着重要作用。然而,参与cBCs自我更新和多能性的小分子调控机制仍不清楚。本研究表明,小分子SC1可在无血清、无饲养层的E8培养基中,在无白血病抑制因子的情况下,将cBCs维持在未分化的多能状态。此外,SC1可抑制视黄酸引起的多能性相关基因的下调,并促进cBCs的增殖。此外,本研究结果表明,SC1通过抑制ERK1磷酸化和促进Akt磷酸化发挥作用,从而促进多能性相关基因的表达并维持cBCs的多能性。结果还表明,SC1通过抑制ERK1磷酸化和促进Akt磷酸化维持cBCs细胞的自我更新能力和多能性。这种调控机制可能在禽类ES细胞中保守。其他类似于SC1的分子可能为控制干细胞命运的分子机制提供见解,并最终有助于体内干细胞生物学和治疗。