Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells
Inhibition of FGF signaling accelerates neural crest cell differentiation of human pluripotent stem cells
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DOI：
10.1016/j.bbrc.2016.10.147
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发表时间：
2016-12-02
影响因子：
3.1
通讯作者：
Noisa, Parinya
中科院分区：
文献类型：
--
作者：
Jaroonwitchawan, Thiranut;Muangchan, Pattamon;Noisa, Parinya
神经嵴（Neural crest， NC）是胚胎发育过程中产生的一种瞬时群体，能够分化为各种体细胞。神经嵴发育缺陷导致神经嵴病变。揭示了几种信号通路在NC细胞分化中的重要意义。成纤维细胞生长因子（Fibroblast growth factor， FGF）在非洲爪蟾和鸟类的NC发育过程中被认为是一个重要的信号传导机制；然而，它对人类物种的贡献仍然难以捉摸。在这里，我们使用人多能干细胞（hPSCs）来研究在NC细胞分化过程中FGF抑制的后果。本研究使用特异性fgf受体抑制剂5135402。抑制FGF不影响hpsc衍生的NC细胞的增殖或死亡，但促进了hpsc的NC细胞命运。nc特异性基因，包括PAX3、SLUG和TWIST'，高度上调，而hPSC基因，如OCT4和E-CAD，在FGF信号阻断后迅速降低。值得注意的是，在su5402诱导的细胞中，大量出现了迁移NC细胞的标记物TFAP-2a。这种加速NC细胞分化可能是由于阻断ERK1/2磷酸化后Notch信号被激活，因为SU5402增加了NICD。综上所述，本研究提出了FGF信号在控制人NC细胞从hPSCs分化中的作用，FGF与Notch之间的串扰，以及FGF信号在神经系统疾病中的影响。(C) 2016 Elsevier Inc.版权所有。
Neural crest (NC) is a transient population, arising during embryonic development and capable of differentiating into various somatic cells. The defects of neural crest development leads to neurocristopathy. Several signaling pathways were revealed their significance in NC cell specification. Fibroblast growth factor (FGF) is recognized as an important signaling during NC development, for instance Xenopus and avian; however, its contributions in human species are remained elusive. Here we used human pluripotent stem cells (hPSCs) to investigate the consequences of FGF inhibition during NC cell differentiation. The specific-FGF receptor inhibitor, 5135402, was used in this investigation. The inhibition of FGF did not found to affect the proliferation or death of hPSC-derived NC cells, but promoted hPSCs to commit NC cell fate. NC-specific genes, including PAX3, SLUG, and TWIST', were highly upregulated, while hPSC genes, such as OCT4, and E-CAD, rapidly reduced upon FGF signaling blockage. Noteworthy, TFAP-2a, a marker of migratory NC cells, abundantly presented in SU5402-induced cells. This accelerated NC cell differentiation could be due to the activation of Notch signaling upon the blockage of ERK1/2 phosphorylation, since NICD was increased by SU5402. Altogether, this study proposed the contributions of FGF signaling in controlling human NC cell differentiation from hPSCs, the crosstalk between FGF and Notch, and might imply to the influences of FGF signaling in neurocristophatic diseases. (C) 2016 Elsevier Inc. All rights reserved.