Akt increases sox2 expression in adult hippocampal neural progenitor cells, but increased sox2 does not promote proliferation.
Akt increases sox2 expression in adult hippocampal neural progenitor cells, but increased sox2 does not promote proliferation.
复制标题
DOI：
10.1089/scd.2010.0130
复制
发表时间：
2011-07
影响因子：
4
通讯作者：
Joseph Peltier;Anthony Conway;Albert J. Keung;D. Schaffer
中科院分区：
文献类型：
--
作者：
Joseph Peltier;Anthony Conway;Albert J. Keung;D. Schaffer
多种细胞外因子已被证明可以调节成年海马神经祖细胞（NPC）的增殖和自我更新，我们以前已经表明，Akt是这些细胞外因子对NPC增殖和分化的影响的重要介质。然而，很少有工作研究Akt如何以及是否参与维持这些细胞的多能性。在这里，我们证明，Akt促进表达Sox 2，一个核心转录因子的自我更新的NPC的重要。逆转录病毒介导的野生型Akt过表达增加Sox 2蛋白表达，特别是在促进细胞分化的条件下，而Akt抑制则降低Sox 2。类似地，在分化培养物中的定量逆转录（RT）-PCR表明Akt将Sox 2 mRNA拯救到在促进细胞增殖的条件下存在的水平。此外，Akt的药理学抑制不影响从逆转录病毒载体组成型表达Sox 2的细胞中的Sox 2蛋白水平，表明Akt不影响Sox 2蛋白稳定性。此外，与Akt过表达相反，Sox 2过表达不增加NPC活细胞数或增殖，但抑制分化。总的来说，这些结果表明Akt通过两个下游途径促进细胞增殖和维持多能状态。
Multiple extracellular factors have been shown to modulate adult hippocampal neural progenitor cell (NPC) proliferation and self-renewal, and we have previously shown that Akt is an important mediator of the effects of these extracellular factors on NPC proliferation and differentiation. However, very little work has investigated how and whether Akt is involved in maintaining the multipotency of these cells. Here we demonstrate that Akt promotes expression of Sox2, a core transcription factor important for the self-renewal of NPCs. Retroviral-mediated overexpression of wild-type Akt increased Sox2 protein expression, particularly under conditions that promote cell differentiation, whereas Akt inhibition decreased Sox2. Similarly, quantitative reverse transcription (RT)-PCR in differentiating cultures indicated that Akt rescued Sox2 mRNA to levels present under conditions that promote cell proliferation. Additionally, pharmacological inhibition of Akt did not affect Sox2 protein levels in cells constitutively expressing Sox2 from a retroviral vector, indicating that Akt does not affect Sox2 protein stability. Further, in contrast to Akt overexpression, Sox2 overexpression does not increase NPC viable cell number or proliferation yet does inhibit differentiation. Collectively, these results indicate that Akt promotes cell proliferation and maintenance of a multipotent state via two downstream paths.