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首页> 外文期刊>BMC Neuroscience >Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells
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Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

机译：Notch信号是维持源自人类胚胎干细胞的神经祖细胞的干细胞特征所必需的

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Background Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs. Results From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo -derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons. Conclusion Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.
机译：背景研究提供了有关Notch信号在神经发育中的作用的重要发现。然而，不幸的是，这些研究大多数都对小鼠或其他实验动物而非人类的神经干细胞（NSC）进行了研究，这主要是由于与获取人脑样本相关的困难。它促使我们专注于源自人类胚胎干细胞（hESC）且被NSC密集居住的神经外胚层球（NESs）。我们在这里研究了Notch信号与hESC衍生的NESs的作用。结果从hESCs，我们获得了NESs，这是脑源性神经球的体外版本。通过各种NSC标记基因水平的提高和已知神经祖细胞驻留的玫瑰花结结构的出现，证实了NES的形成。我们发现，Notch信号能够维持源自体内的神经祖细胞的干细胞特性，在这些源自hESC的NES中具有活性，类似于其体内对应物。 NES中Notch信号分子如NICD，DLL，JAG1，HES1和HES5的表达水平增加。 γ-分泌酶抑制剂对Notch信号的抑制作用降低了玫瑰花结的结构，NSC标记基因的表达水平以及NES中的增殖潜能，并且如果与生长因子的撤除结合，则引发了向神经元的分化。结论我们的结果表明，与脑源性神经球具有生化特性的hESC衍生的NESs主要通过Notch信号维持干细胞特性，这表明hESC衍生的NESs可能是体内神经发生的体外模型。 。

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