Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine, 200025 Shanghai, China.
J Cell Biol. 2013 Apr 29;201(3):409-25. doi: 10.1083/jcb.201207172.
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.
成体干细胞（ASCs）具有自我更新和分化的能力，使组织具有再生受损部位的潜力。表观遗传调控对于通过快速和可逆地调节基因表达程序来驱动细胞命运决定至关重要。然而，目前尚不清楚表观遗传因子如何引发 ASC 驱动的再生。在本文中，我们报告说，针对 205 个染色质调节剂的 RNA 干扰筛选鉴定出了 12 种对涡虫 ASC 功能和再生至关重要的蛋白质。令人惊讶的是，HP1 样蛋白 SMED-HP1-1（HP1-1）特异性标记自我更新的多能 ASC，并且 HP1-1 耗竭会破坏自我更新并促进分化。在受伤时，HP1-1 的表达增加，并通过与 FACT（促进染色质转录）复合物的功能关联，引起 ASC 中 Mcm5 的表达增加，从而引发 ASC 的增殖并启动芽基形成。我们的观察结果揭示了一个在涡虫中调控 ASC 的表观遗传网络，并表明 HP1 蛋白是控制干细胞功能的关键染色质因子。这些结果为我们提供了重要的见解，即表观遗传机制如何在组织再生过程中协调干细胞反应。
