Human motor neuron differentiation from human embryonic stem cells
Human motor neuron differentiation from human embryonic stem cells
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DOI：
10.1089/scd.2005.14.266
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发表时间：
2005-06-01
影响因子：
4
通讯作者：
Stice, SL
中科院分区：
文献类型：
--
作者：
Shin, S;Dalton, S;Stice, SL
胚胎干细胞（ES）的治疗潜力是有希望的，但在许多情况下，由于我们无法促进它们分化为特定的细胞类型，如运动神经元，因此受到限制。在这里，我们提供了人类胚胎干细胞成功分化为运动神经元表型细胞的第一份报告。从人类胚胎干细胞中产生了一种可再生的神经上皮细胞。然后利用细胞外信号诱导这些细胞的运动神经元分化和相关基因表达。在加入碱性成纤维细胞生长因子、视黄酸和超音hedgehog基因后，OLIG2和HLXB9基因表达增加，并形成表达Islet1和胆碱乙酰转移酶（choline acetyltransferase, ChAT）的运动神经元表型。这项研究表明，来源于人类胚胎干细胞的神经上皮细胞是可再生的祖细胞，能够产生运动神经元，其水平可能在治疗上有用。Sonic hedgehog、碱性成纤维细胞生长因子和视黄酸对人类运动神经元分化的不同影响机制仍有待明确。
The therapeutic potential of embryonic stem (ES) cells is promising, but in many cases limited by our inability to promote their differentiation to specific cell types, such as motor neurons. Here we provide the first report of the successful differentiation of human ES cells to cells of a motor neuron phenotype. A renewable source of neuroepithelial cells was generated from human ES cells. Extracellular signals were then employed to induce motor neuron differentiation and related gene expression by these cells. OLIG2 and HLXB9 gene expression increased upon the addition of basic fibroblast growth factor, retinoic acid, and sonic hedgehog, as a motor neuron phenotype expressing Islet1 and choline acetyltransferase ( ChAT) developed. This study demonstrates that neuroepithelial cells derived from human ES cells are renewable progenitors capable of generating motor neurons at levels that may be therapeutically useful. Sonic hedgehog, basic fibroblast growth factor, and retinoic acid differentially influence human motor neuron differentiation by mechanisms that remain to be defined.