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UV-induced reduction in Polycomb repression promotes epidermal pigmentation
Developmental Cell ( IF 10.7 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.devcel.2021.08.006
Meng-Yen Li 1 , Pooja Flora 1 , Hong Pu 2 , Carmit Bar 1 , Jose Silva 3 , Idan Cohen 4 , Phillip M Galbo 5 , Hequn Liu 5 , Xufen Yu 6 , Jian Jin 6 , Haruhiko Koseki 7 , John A D'Orazio 2 , Deyou Zheng 8 , Elena Ezhkova 1
Affiliation  

Ultraviolet (UV) radiation is a prime environmental stressor that our epidermis is exposed to on a daily basis. To avert UV-induced damage, epidermal stem cells (EpSCs) become pigmented via a process of heterotypic interaction between melanocytes and EpSCs; however, the molecular mechanisms of this interaction are not well understood. In this study, we show that the function of a key chromatin regulator, the Polycomb complex, was reduced upon UV exposure in human and mouse epidermis. Genetic ablation of key Polycomb subunits in murine EpSCs, mimicking depletion upon UV exposure, results in an increased number of epidermal melanocytes and subsequent epidermal pigmentation. Genome-wide transcriptional and chromatin studies show that Polycomb regulates the expression of UV-responsive genes and identifies type II collagen (COL2A1) as a critical secreted regulator of melanogenesis and epidermal pigmentation. Together, our findings show how UV exposure induces Polycomb-mediated changes in EpSCs to affect melanocyte behavior and promote epidermal pigmentation.



中文翻译:


紫外线诱导的多梳抑制减少促进表皮色素沉着



紫外线 (UV) 辐射是我们的表皮每天暴露的主要环境压力源。为了避免紫外线引起的损伤,表皮干细胞 (EpSC) 通过黑素细胞和 EpSC 之间的异型相互作用过程产生色素;然而,这种相互作用的分子机制尚不清楚。在这项研究中,我们发现,在人和小鼠表皮中,关键染色质调节因子 Polycomb 复合物的功能在受到紫外线照射后会降低。对小鼠 EpSC 中关键的 Polycomb 亚基进行基因消融,模拟紫外线照射后的消耗,导致表皮黑素细胞数量增加,并随后导致表皮色素沉着。全基因组转录和染色质研究表明,Polycomb 调节紫外线响应基因的表达,并将 II 型胶原蛋白 (COL2A1) 确定为黑素生成和表皮色素沉着的关键分泌调节剂。总之,我们的研究结果表明,紫外线暴露如何诱导 EpSC 中 Polycomb 介导的变化,从而影响黑素细胞行为并促进表皮色素沉着。

更新日期:2021-09-28
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