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全反式维甲酸通过多种途径促进多能胚胎干细胞进入神经谱系。

All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways.

作者信息

Lu Jianfeng, Tan Li, Li Ping, Gao Hui, Fang Bo, Ye Shoudong, Geng Zhe, Zheng Ping, Song Houyan

机构信息

Department of Molecular Genetics, Shanghai Medical School, Fudan University, Shanghai, PR China.

出版信息

BMC Cell Biol. 2009 Jul 30;10:57. doi: 10.1186/1471-2121-10-57.

DOI:10.1186/1471-2121-10-57
PMID:19642999
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2728515/
Abstract

BACKGROUND

All-trans retinoic acid (RA) is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs), we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture.

RESULTS

Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF) signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK) pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation.

CONCLUSION

RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

摘要

背景

全反式维甲酸（RA）是具有多效性作用的最重要的形态发生素之一。其在胚胎中的分布与发育中的中枢神经系统的神经分化相关。为了探究RA对小鼠胚胎干细胞（ESC）神经分化的确切影响，我们检测了小鼠ESC中RA核受体和RA代谢酶的表达，并研究了RA在贴壁单层培养中的作用。

结果

添加RA后，细胞分化迅速且仅定向为神经谱系。相反，对RA信号的药理学干扰抑制了这种神经分化。抑制成纤维细胞生长因子（FGF）信号在RA处理的培养物中并未显著抑制神经分化。对细胞外信号调节激酶（ERK）途径的药理学干扰或Wnt途径的激活有效地阻断了RA促进的神经特化。在分化早期，RA处理的培养物中ERK磷酸化增强。

结论

在贴壁单层培养系统中，RA可促进ESC进入神经谱系。这种作用取决于RA信号及其与ERK和Wnt途径的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/830d8cd66a07/1471-2121-10-57-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/264482bf4805/1471-2121-10-57-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/f173bd5c673f/1471-2121-10-57-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/d5f121730927/1471-2121-10-57-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/e55111acdeff/1471-2121-10-57-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/2fb44234aa0c/1471-2121-10-57-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/830d8cd66a07/1471-2121-10-57-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/264482bf4805/1471-2121-10-57-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/f173bd5c673f/1471-2121-10-57-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/d5f121730927/1471-2121-10-57-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/e55111acdeff/1471-2121-10-57-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/2fb44234aa0c/1471-2121-10-57-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dbd/2728515/830d8cd66a07/1471-2121-10-57-6.jpg

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