Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development.
Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development.
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解剖Polycomb抑制复合物在皮肤发育中的控制中的作用。
DOI：
10.1016/j.jid.2016.02.809
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Ezhkova E
中科院分区：
文献类型：
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作者：
Dauber KL;Perdigoto CN;Valdes VJ;Santoriello FJ;Cohen I;Ezhkova E
多梳抑制复合物2（PRC 2）是细胞生理学的重要调节因子。虽然已经有许多关于PRC 2在体细胞组织发育和干细胞控制中的功能的研究，但这些研究都集中在单个PRC 2亚基的丢失上。然而，最近的研究表明，PRC 2亚基可能独立于PRC 2复合物发挥作用。为了研究PRC 2在控制皮肤发育中的功能，我们产生并分析了三种条件性基因敲除小鼠品系，其中PRC 2的必需亚基EED、Suz 1/2或Ezh 1/2在胚胎表皮祖细胞中被条件性地切除，所述胚胎表皮祖细胞产生表皮、毛囊和默克尔细胞。我们的研究表明，所观察到的功能丧失表型在三种基因敲除之间是共享的，这表明在皮肤上皮中，EED、Suz 1/2和Ezh 1/2主要作为PRC 2复合物的亚基起作用。有趣的是，PRC 2的缺失导致不同皮肤谱系中显著不同的表型：功能性表皮屏障的过早获得、异位默克尔细胞的形成以及毛囊的出生后发育缺陷。PRC 2在三种谱系形成中的显著不同的作用说明了在体干细胞系统中缺乏PRC 2可能产生的复杂结果。
Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. While there have been numerous studies on PRC2 function in somatic tissue development and stem cell control, these have focused on the loss of a single PRC2 subunit. Recent studies, however, have shown that PRC2 subunits may function independently of the PRC2 complex. To investigate the function of PRC2 in the control of skin development, we generated and analysed three conditional knockout mouse lines, in which the essential PRC2 subunits EED, Suz12, or Ezh1/2 are conditionally ablated in the embryonic epidermal progenitors that give rise to the epidermis, hair follicles, and Merkel cells. Our studies showed that the observed loss-of-function phenotypes are shared between the three knockouts, indicating that in the skin epithelium, EED, Suz12, and Ezh1/2 function largely as subunits of the PRC2 complex. Interestingly, the absence of PRC2 results in dramatically different phenotypes across the different skin lineages: premature acquisition of a functional epidermal barrier, formation of ectopic Merkel cells, and defective postnatal development of hair follicles. The strikingly different roles of PRC2 in the formation of three lineages exemplify the complex outcomes that the lack of PRC2 can have in a somatic stem cell system.