Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling.

Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling.
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DOI:
10.1111/j.1365-2443.2010.01413.x
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发表时间:
2010-06
期刊:
Genes to cells : devoted to molecular & cellular mechanisms
影响因子:
--
通讯作者:
Kageyama R
Kageyama R
中科院分区:
其他
文献类型:
--
作者:
Kobayashi T;Kageyama R

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胚胎干(ES)细胞在诱导分化时表现出异质反应。最近的分析表明,小鼠 ES 细胞中 Hes1 表达的振荡周期约为 3-5 小时,这种振荡表达导致异质性反应:Hes1 高的 ES 细胞倾向于中胚层命运,而 Hes1 低的 ES 细胞倾向于神经命运。 Hes1-high 和 Hes1-low ES 细胞的这些结果分别与 Notch 信号失活和激活的结果非常相似。这些结果表明,Hes1 和 Notch 信号传导在 ES 细胞分化中导致相反的结果,尽管它们在大多数其他细胞类型中以相同的方向发挥作用。在这里,我们发现 Hes1 在 ES 细胞分化中充当 Notch 信号传导的抑制剂,而不是效应器。我们的结果表明,持续的 Hes1 表达延迟了 ES 细胞的分化,并通过抑制 Notch 信号传导促进对中胚层而不是神经命运的偏好。
Embryonic stem (ES) cells display heterogeneous responses upon induction of differentiation. Recent analysis has shown that Hes1 expression oscillates with a period of about 3–5 h in mouse ES cells and that this oscillating expression contributes to the heterogeneous responses: Hes1-high ES cells are prone to the mesodermal fate, while Hes1-low ES cells are prone to the neural fate. These outcomes of Hes1-high and Hes1-low ES cells are very similar to those of inactivation and activation of Notch signaling, respectively. These results suggest that Hes1 and Notch signaling lead to opposite outcomes in ES cell differentiation, although they work in the same direction in most other cell types. Here, we found that Hes1 acts as an inhibitor but not as an effector of Notch signaling in ES cell differentiation. Our results indicate that sustained Hes1 expression delays the differentiation of ES cells and promotes the preference for the mesodermal rather than the neural fate by suppression of Notch signaling.
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