Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells.
Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells.
复制标题
异染色质蛋白 1 促进成体干细胞的自我更新并触发再生增殖
DOI：
10.1083/jcb.201207172
复制
发表时间：
2013-04-29
期刊：
影响因子：
--
通讯作者：
Jing Q
中科院分区：
文献类型：
--
作者：
Zeng A;Li YQ;Wang C;Han XS;Li G;Wang JY;Li DS;Qin YW;Shi Y;Brewer G;Jing Q
涡虫染色质调节因子HP1，至少在一定程度上通过Mcm5的表达增加起作用，抑制成体干细胞的分化，并在损伤反应中触发它们的增殖。成体干细胞（ASCs）能够自我更新和分化，赋予组织再生受损部位的潜力。表观遗传调控是必不可少的驱动细胞命运决定通过快速和可逆调节基因表达程序。然而，目前尚不清楚表观遗传因素如何引发asc驱动的再生。在本文中，我们报道了针对205个染色质调节因子的RNA干扰筛选，鉴定了涡虫ASC功能和再生所必需的12种蛋白质。令人惊讶的是，hp1样蛋白SMED-HP1-1 （HP1-1）特异性标记自我更新、多能ASCs，而HP1-1耗竭则消除自我更新并促进分化。损伤后，HP1-1表达增加，并通过与FACT（促进染色质转录）复合物的功能关联引发Mcm5 ASC表达增加，从而触发ASC增殖并启动胚质形成。我们的观察结果揭示了涡虫ASC调控的表观遗传网络，并揭示了HP1蛋白是控制干细胞功能的关键染色质因子。这些结果为研究表观遗传机制如何在组织再生过程中协调干细胞反应提供了重要的见解。
The planarian chromatin regulator HP1, at least in part acting through increased expression of Mcm5, inhibits differentiation of adult stem cells and triggers their proliferation in response to injury. Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED–HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration.
登录
查看更多内容
影响因子：
4.5
作者：
Houlard, Martin;Berlivet, Soizik;Probst, Aline V.;Quivy, Jean-Pierre;Hery, Patrick;Almouzni, Genevieve;Gerard, Matthieu
通讯作者：
Gerard, Matthieu
影响因子：
10.5
作者：
Kwon, So Hee;Florens, Laurence;Workman, Jerry L.
通讯作者：
Workman, Jerry L.
影响因子：
10.5
作者：
Cammas, F;Herzog, M;Losson, R
通讯作者：
Losson, R
影响因子：
23.9
作者：
Cui K;Zang C;Roh TY;Schones DE;Childs RW;Peng W;Zhao K
通讯作者：
Zhao K
影响因子：
5.2
作者：
Labbe, Roselyne M.;Irimia, Manuel;Currie, Ko W.;Lin, Alexander;Zhu, Shu Jun;Brown, David D. R.;Ross, Eric J.;Voisin, Veronique;Bader, Gary D.;Blencowe, Benjamin J.;Pearson, Bret J.
通讯作者：
Pearson, Bret J.