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首页> 外文期刊>EMBO Journal >Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells
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Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells

机译：Polycomb子单元Ezh1 Ezh2调节默克尔在皮肤干细胞细胞分化项目细胞

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While the Polycomb complex is known to regulate cell identity in ES cells, its role in controlling tissue-specific stem cells is not well understood. Here we show that removal of Ezh1 and Ezh2, key Polycomb subunits, from mouse skin results in a marked change in fate determination in epidermal progenitor cells, leading to an increase in the number of lineage-committed Merkel cells, a specialized subtype of skin cells involved in mechanotransduction. By dissecting the genetic mechanism, we showed that the Polycomb complex restricts differentiation of epidermal progenitor cells by repressing the transcription factor Sox2. Ablation of Sox2 results in a dramatic loss of Merkel cells, indicating that Sox2 is a critical regulator of Merkel cell specification. We show that Sox2 directly activates Atoh1, the obligate regulator of Merkel cell differentiation. Concordantly, ablation of Sox2 attenuated the Ezh1/2-null phenotype, confirming the importance of Polycomb-mediated repression of Sox2 in maintaining the epidermal progenitor cell state. Together, these findings define a novel regulatory network by which the Polycomb complex maintains the progenitor cell state and governs differentiation in vivo.
机译：虽然Polycomb复杂的调节细胞的身份在ES细胞,其作用控制组织干细胞不是很好理解。Ezh1 Ezh2,关键Polycomb子单元,从鼠标皮肤明显改变命运决心在表皮祖细胞,导致增加的数量lineage-committed默克尔细胞,一个专业皮肤细胞参与的亚型转导。机制,我们表明,Polycomb复杂限制了分化表皮祖抑制细胞的转录因子Sox2。默克尔细胞,这表明Sox2是a默克尔细胞规范的关键调节器。我们表明,直接激活Atoh1 Sox2,专性监管机构默克尔细胞分化。减毒Ezh1/2-null表型,确认Polycomb-mediated镇压的重要性Sox2在维持表皮祖细胞状态。Polycomb复杂的监管网络维护祖细胞状态和控制体内分化。

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