Stromal Cell-Secreted Factors Promote the Survival of Embryonic Stem Cell-Derived Early Neural Stem/Progenitor Cells Via the Activation of MAPK and PI3K-Akt Pathways
Stromal Cell-Secreted Factors Promote the Survival of Embryonic Stem Cell-Derived Early Neural Stem/Progenitor Cells Via the Activation of MAPK and PI3K-Akt Pathways
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DOI：
10.1002/jnr.22250
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发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Ishii, Seiji;Okada, Yohei;Okano, Hideyuki
神经干/祖细胞（neural stem/progenitor cells，NS/PCs）被广泛研究，并有望应用于临床修复受损的中枢神经系统。然而，很少有人知道的信号，调节NS/PC的增殖，存活和分化的早期发展。为了阐明潜在的机制，我们利用了在体外ES细胞分化系统，我们可以获得神经球含有NS/PC的早期尾神经管的特征，通过处理胚状体（EBs）与低浓度的视黄酸（RA）。我们发现，条件培养基从PA 6基质细胞系（PA 6CM）增加了效率的神经球形成抑制凋亡和促进NS/PC的生存。PA 6CM还诱导来源于ES细胞的细胞中Erk 1/2和Akt 1的磷酸化。此外，MAPK和PI 3 K-Akt信号通路的抑制剂U 0126和LY 294002减弱了PA 6CM的作用，显著增加了ES细胞来源的NS/PC中的凋亡细胞的数量，并减少了存活细胞的数量。因此，PA 6CM似乎含有可溶性因子，其通过激活MAP K和PI 3 K-Akt途径促进ES细胞衍生的早期NS/PC的存活。(C)2009 wiley-Liss，Inc.
Neural stem/progenitor cells (NS/PCs) have been studied extensively with the hope of using them clinically to repair the damaged central nervous system. However, little is known about the signals that regulate the proliferation, survival, and differentiation of NS/PCs in early development. To clarify the underlying mechanisms, we took advantage of an in vitro ES cell differentiation system from which we can obtain neurospheres containing NS/PCs with characteristics of the early caudal neural tube, by treating embryoid bodies (EBs) with a low concentration of retinoic acid (RA). We found that conditioned medium from the PA6 stromal cell line (PA6CM) increased the efficiency of neurosphere formation by suppressing apoptosis and promoting the survival of the NS/PCs. PA6CM also induced the phosphorylation of Erk1/2 and Akt1 in cells derived from the EBs Furthermore, inhibitors of the MAPK and PI3K-Akt signaling pathways, U0126 and LY294002, attenuated the effects of PA6CM, significantly increasing the number of apoptotic cells and decreasing the number of viable cells among the ES cell-derived NS/PCs. Thus, PA6CM appears to contain soluble factors that promote the survival of ES cell-derived early NS/PCs through the activation of the MAP K and PI3K-Akt pathways. (C) 2009 wiley-Liss, Inc.