Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, 00185, Rome, Italy.
Istituto Pasteur Italia, Fondazione Cenci-Bolognetti, 00185, Rome, Italy.
Sci Rep. 2019 Mar 13;9(1):4372. doi: 10.1038/s41598-019-40152-1.
A very important open question in stem cells regulation is how the fine balance between GSCs self-renewal and differentiation is orchestrated at the molecular level. In the past several years much progress has been made in understanding the molecular mechanisms underlying intrinsic and extrinsic controls of GSC regulation but the complex gene regulatory networks that regulate stem cell behavior are only partially understood. HP1 is a dynamic epigenetic determinant mainly involved in heterochromatin formation, epigenetic gene silencing and telomere maintenance. Furthermore, recent studies have revealed the importance of HP1 in DNA repair, sister chromatid cohesion and, surprisingly, in positive regulation of gene expression. Here, we show that HP1 plays a crucial role in the control of GSC homeostasis in Drosophila. Our findings demonstrate that HP1 is required intrinsically to promote GSC self-renewal and progeny differentiation by directly stabilizing the transcripts of key genes involved in GSCs maintenance.
干细胞调控中一个非常重要的开放性问题是，在分子水平上如何精细地协调 GSCs 自我更新和分化之间的平衡。在过去的几年中，人们在理解内在和外在控制 GSC 调控的分子机制方面取得了很大进展，但对调控干细胞行为的复杂基因调控网络的理解还只是部分的。HP1 是一种动态的表观遗传决定因素，主要参与异染色质形成、表观遗传基因沉默和端粒维持。此外，最近的研究揭示了 HP1 在 DNA 修复、姐妹染色单体黏合以及令人惊讶的是在基因表达的正向调控中的重要性。在这里，我们表明 HP1 在控制果蝇 GSC 动态平衡中起着关键作用。我们的研究结果表明，HP1 内在地需要通过直接稳定参与 GSCs 维持的关键基因的转录本，来促进 GSC 的自我更新和后代分化。
