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从人类胚胎干细胞中生成中组织者样细胞。

Generation of Isthmic Organizer-Like Cells from Human Embryonic Stem Cells.

机构信息

Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Korea.

Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea.

出版信息

Mol Cells. 2018 Feb 28;41(2):110-118. doi: 10.14348/molcells.2018.2210. Epub 2018 Jan 31.

DOI:10.14348/molcells.2018.2210
PMID:29385674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5824020/
Abstract

The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 (0.6 μM) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course . Resultant cells showed upregulated expression levels of and . The addition of exogenous FGF8 further increased expression by 2.6 fold. Gene ontology following microarray analysis confirmed that IsO-like cells enriched the expression of MHB-related genes by 40 fold compared to control cells. Lysates and conditioned media of IsO-like cells contained functional FGF8 and WNT1 proteins that could induce MHB-related genes in differentiating ESCs. The method for generating functional IsO-like cells described in this study could be used to study human central nervous system development and congenital malformations of the midbrain and hindbrain.

摘要

本研究的目的是诱导产生能够分泌成纤维细胞生长因子 (FGF) 8 和 WNT1 的坐骨体组织者 (IsO)-样细胞。在小分子 CHIR99021（0.6 μM）存在的情况下，精确调节经典 Wnt 信号，从而在人类胚胎干细胞 (ESC) 的神经诱导过程中，将这些细胞分化为具有中脑-后脑边界 (MHB) 命运的 IsO-样细胞，以重现其发育过程。结果细胞显示上调表达的 和 。添加外源性 FGF8 可使 表达进一步增加 2.6 倍。微阵列分析后的基因本体确认，与对照细胞相比，IsO-样细胞富集了 MHB 相关基因的表达，富集倍数为 40 倍。IsO-样细胞的裂解物和条件培养基含有功能 FGF8 和 WNT1 蛋白，可诱导分化中的 ESC 中与 MHB 相关的基因表达。本研究中生成功能性 IsO-样细胞的方法可用于研究人类中枢神经系统发育以及中脑和后脑的先天性畸形。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/9a3a58484245/molce-41-2-110f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/b91cbf52abc3/molce-41-2-110f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/cf834554299a/molce-41-2-110f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/15043caf83ac/molce-41-2-110f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/bc15802d8443/molce-41-2-110f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/9a3a58484245/molce-41-2-110f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/b91cbf52abc3/molce-41-2-110f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/cf834554299a/molce-41-2-110f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/15043caf83ac/molce-41-2-110f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/bc15802d8443/molce-41-2-110f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6287/5824020/9a3a58484245/molce-41-2-110f5.jpg

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本文引用的文献

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从多能性到前脑模式形成：借助胚胎干细胞的体外研究历程
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