Polycomb repressive complex 2 in adult hair follicle stem cells is dispensable for hair regeneration.
Polycomb repressive complex 2 in adult hair follicle stem cells is dispensable for hair regeneration.
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DOI：
10.1371/journal.pgen.1009948
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发表时间：
2021-12
期刊：
影响因子：
4.5
通讯作者：
Ezhkova E
中科院分区：
文献类型：
--
作者：
Flora P;Li MY;Galbo PM Jr;Astorkia M;Zheng D;Ezhkova E
毛囊干细胞（HFSC）是多能细胞，其通过静止和活化循环以持续地促进毛囊的产生。先前的基因组作图研究已经表明，组蛋白H3在赖氨酸27（H3 K27 me 3）处的三甲基化，由多梳抑制复合物2（PRC 2）介导的染色质标记，在静止和活化的HFSC之间是动态的，这表明与H3 K27 me 3相关的转录变化可能对HFSC的正常功能至关重要。然而，缺乏阐明PRC 2在成人HFSC中的作用的功能性体内研究。在这项研究中，通过使用体内功能丧失研究，我们发现，令人惊讶的是，PRC 2在成人HFSC中起着非指导性作用，并且HFSC中PRC 2的丧失不会导致HFSC静止期的丧失或细胞特性的变化。有趣的是，PRC 2无效的静止HFSC的RNA-seq和免疫荧光分析揭示了与HFSC的活化状态相关的基因的上调。总之，我们的研究结果表明，PRC 2调控下的转录程序是维持HFSC静止和毛发再生的关键。毛囊干细胞（HFSC）具有令人难以置信的能力，可以通过静止和激活来循环，从而在生物体的整个生命周期中为毛囊的产生提供燃料。在毛发生长开始期间，HFSC经历短暂活化以增殖，但在毛发周期的剩余阶段迅速恢复到其静止状态。HFSC激活和静止之间的这种平衡是通过建立一个特定的转录景观来维持的;然而，关于染色质修饰因子（基因转录的关键调节因子）如何控制成人HFSC功能知之甚少。先前的基因组作图研究表明，H3 K27 me 3，由多梳抑制复合物2（PRC 2）介导的染色质标记，在静止和激活的HFSC之间是动态的，这表明与H3 K27 me 3相关的转录变化可能对HFSC的正常功能至关重要。尽管存在这种相关性，但缺乏阐明PRC 2在成人HFSC中作用的体内功能研究。在这项研究中，我们表明，PRC 2在成人HFSC中的消融导致适度的转录变化，这些变化不足以改变HFSC的命运或功能，从而产生生理相关的影响，这表明其他染色质调节机制可能会保护成人HFSC的功能和身份。
Hair follicle stem cells (HFSCs) are multipotent cells that cycle through quiescence and activation to continuously fuel the production of hair follicles. Prior genome mapping studies had shown that tri-methylation of histone H3 at lysine 27 (H3K27me3), the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. However, functional in vivo studies elucidating the role of PRC2 in adult HFSCs are lacking. In this study, by using in vivo loss-of-function studies we show that, surprisingly, PRC2 plays a non-instructive role in adult HFSCs and loss of PRC2 in HFSCs does not lead to loss of HFSC quiescence or changes in cell identity. Interestingly, RNA-seq and immunofluorescence analyses of PRC2-null quiescent HFSCs revealed upregulation of genes associated with activated state of HFSCs. Altogether, our findings show that transcriptional program under PRC2 regulation is dispensable for maintaining HFSC quiescence and hair regeneration. Hair follicle stem cells (HFSCs) have the incredible capacity to cycle through quiescence and activation to fuel the production of hair follicles throughout the life of an organism. During the onset of hair growth, HFSCs undergo transient activation to proliferate but quickly revert to their quiescent state for the remaining of the hair cycle phases. This balance between HFSC activation and quiescence is maintained by establishing a specific transcriptional landscape; however, very little is known about how chromatin-modifying factors, critical regulators of gene transcription, control adult HFSC function. Prior genome mapping studies had shown that H3K27me3, the chromatin mark mediated by Polycomb Repressive Complex 2 (PRC2), is dynamic between quiescent and activated HFSCs, suggesting that transcriptional changes associated with H3K27me3 might be critical for proper HFSC function. Despite this correlation, functional in vivo studies elucidating the role of PRC2 in adult HFSCs were lacking. In this study, we show that ablation of PRC2 in the adult HFSCs leads to modest transcriptional changes that are insufficient to alter HFSC fate or function to have physiologically relevant effects, indicating that other chromatin regulatory mechanisms could be safeguarding adult HFSC function and identity.
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紫外线诱导的多康布抑制作用促进表皮色素沉着。
影响因子：
11.8
作者：
Li MY;Flora P;Pu H;Bar C;Silva J;Cohen I;Galbo PM Jr;Liu H;Yu X;Jin J;Koseki H;D'Orazio JA;Zheng D;Ezhkova E
通讯作者：
Ezhkova E
影响因子：
16.6
作者：
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通讯作者：
Tumbar T
影响因子：
10.5
作者：
Cohen I;Bar C;Liu H;Valdes VJ;Zhao D;Galbo PM Jr;Silva JM;Koseki H;Zheng D;Ezhkova E
通讯作者：
Ezhkova E
影响因子：
23.9
作者：
Lien, Wen-Hui;Guo, Xingyi;Polak, Lisa;Lawton, Lee N.;Young, Richard A.;Zheng, Deyou;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
DOI：
10.1038/nrm4067
发表时间：
2015-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Blackledge NP;Rose NR;Klose RJ
通讯作者：
Klose RJ