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Role of voltage-gated potassium channels in the fate determination of embryonic stem cells.

机译:电压门控钾通道的作用胚胎干细胞的命运的决心。

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Embryonic stem cells (ESCs) possess two unique characteristics: self-renewal and pluripotency. In this study, roles of voltage-gated potassium channels (K(v)) in maintaining mouse (m) ESC characteristics were investigated. Tetraethylammonium (TEA(+)), a K(v) blocker, attenuated cell proliferation in a concentration-dependent manner. Possible reasons for this attenuation, including cytotoxicity, cell cycle arrest and differentiation, were examined. Blocking K(v) did not change the viability of mESCs. Interestingly, K(v) inhibition increased the proportion of cells in G(0)/G(1) phase and decreased that in S phase. This change in cell cycle distribution can be attributed to cell cycle arrest or differentiation. Loss of pluripotency as determined at both molecular and functional levels was detected in mESCs with K(v) blockade, indicating that K(v) inhibition in undifferentiated mESCs directs cells to differentiate instead of to self-renew and progress through the cell cycle. Membrane potential measurement revealed that K(v) blockade led to depolarization, consistent with the role of K(v) as the key determinant of membrane potential. The present results suggest that membrane potential changes may act as a "switch" for ESCs to decide whether to proliferate or to differentiate: hyperpolarization at G(1) phase would favor ESCs to enter S phase while depolarization would favor ESCs to differentiate. Consistent with this notion, S-phase-synchronized mESCs were found to be more hyperpolarized than G(0)/G(1)-phase-synchronized mESCs. Moreover, when mESCs differentiated, the differentiation derivatives depolarized at the initial stage of differentiation. This investigation is the first study to provide evidence that K(v) and membrane potential affect the fate determination of ESCs.
机译:胚胎干细胞(ESCs)拥有两个独一无二的特点:自我更新和多潜能。在这项研究中,角色的电压门控钾通道(K (v))在维持小鼠ESC (m)特征进行调查。四乙铵(茶(+))、K (v)拦截器,减毒细胞增殖浓度的方式。对于这个衰减,包括细胞毒性,细胞周期阻滞和分化检查。制的可行性。抑制细胞的比例增加G (0) / G(1)阶段和下降,在S期。这种变化在细胞周期分布归因于细胞周期阻滞或分化。在分子和功能决定的水平检测与K (v)封锁,制表明K (v)的抑制作用未分化的制指导细胞代替自我更新和分化通过细胞周期进展。潜在的测量表明,K (v)封锁导致去极化,与作用一致K (v)的膜的关键因素的潜力。膜电位的变化可以作为一个“开关”ESCs决定是否扩散区分:超极化在G(1)阶段将有利于ESCs进入S期去极化会忙的ESCs区分。符合这个概念,S-phase-synchronized制被认为是超极化比G (0) / G (1) -phase-synchronized制。当公司的差异化,差异化衍生工具去极化的初始阶段分化。研究提供证据表明,K (v)和膜潜在影响的ESCs的命运的决心。

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