Characterization of conserved post-transcriptional mechanisms regulating stem cells in planarians and mice

涡虫和小鼠干细胞保守转录后机制的表征

• 批准号: 266026236
• 负责人: Professorin Dr. Kerstin Bartscherer
• 金额: --
• 依托单位: Guangzhou Institute of Biomedicine and Health (GIBH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/266026236?language=en
• 关键词: Characterization; conserved; post; transcriptional; mechanisms

Pluripotency describes the potential of a cell to give rise to all cell types of an organism. It has been mainly studied in cultured cells derived from embryonic tissues or from somatic cells through iPS technology. However, these cells are deprived of their natural environment and lack important interactions within a stem cell niche through extracellular molecules. In the presented study, we aim to identify and investigate conserved regulatory networks and mechanisms that control stem cell behaviour in vivo. We will use the stem cell systems of two model organisms, planarian adult stem cells and mouse male germline stem cells, which share remarkable features of developmental pluripotency and regenerative power. With the two experimental systems we will be able to go beyond commonly used in vitro culture systems and use planarians and mice as in vivo Petri dishes for research on pluripotent stem cells. Given that posttranscriptional mechanisms for regulating stem cells have been largely neglected, we will establish these processes as crucial players in the control of pluripotency. Using bioinformatics analyses of previous expression data, genes encoding proteins with putative RNA binding motifs and their potential regulatory networks will be identified. Taking advantage of fast and efficient gene silencing by RNA interference (RNAi) in planarians and the recently developed CRISPR/Cas9 gene editing system in mouse, conserved RNA regulating genes will be analyzed for their functions and interaction partners in planarian adult stem cells and mouse spermatogonial stem cells (SSCs). Our study will provide important insights into post-transcriptional mechanisms that control self-renewal versus differentiation of adult stem cells and provide bases for their biomedical exploitation for enhancing tissue regeneration and treating male infertility.

多能性描述了细胞产生生物体所有细胞类型的潜力。它主要在来自胚胎组织或通过iPS技术来自体细胞的培养细胞中进行研究。然而，这些细胞被剥夺了它们的自然环境，并且缺乏通过细胞外分子在干细胞生态位内的重要相互作用。在本研究中，我们的目的是确定和调查保守的调控网络和机制，控制干细胞在体内的行为。我们将使用两种模式生物的干细胞系统，即真涡虫成体干细胞和小鼠雄性生殖系干细胞，它们具有发育多能性和再生能力的显著特征。有了这两个实验系统，我们将能够超越常用的体外培养系统，使用真涡虫和小鼠作为体内培养皿，用于多能干细胞的研究。鉴于调节干细胞的转录后机制在很大程度上被忽视，我们将建立这些过程作为控制多能性的关键球员。使用生物信息学分析以前的表达数据，基因编码蛋白质与假定的RNA结合基序和他们的潜在的监管网络将被确定。利用RNA干扰（RNAi）在真涡虫中快速有效的基因沉默和最近开发的小鼠CRISPR/Cas9基因编辑系统，将分析保守的RNA调控基因在真涡虫成体干细胞和小鼠精原干细胞（SSC）中的功能和相互作用伙伴。我们的研究将为控制成体干细胞自我更新与分化的转录后机制提供重要的见解，并为它们用于增强组织再生和治疗男性不育的生物医学开发提供基础。

项目成果

The Integrator complex regulates differential snRNA processing and fate of adult stem cells in the highly regenerative planarian Schmidtea mediterranea

Integrator 复合物调节高度再生涡虫 Schmidtea mediterranea 中成体干细胞的差异 snRNA 加工和命运

• DOI: 10.1371/journal.pgen.1007828
• 发表时间: 2018
• 期刊: PLoS Genetics
• 影响因子: 4.5
• 作者: Schmidt D;Reuter H;Hüttner K;Ruhe L;Rabert F;Seebeck F;Irimia M;Solana J;Bartscherer K
• 通讯作者: Bartscherer K