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Adding a dimension to cell fate

机译：为细胞命运添加维度

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Cell fate specification, gene expression and spatial restriction are process finely tuned by epigenetic regulatory mechanisms. At the same time, mechanical forces have been shown to be crucial to drive cell plasticity and boost differentiation. Indeed, several studies have demonstrated that transitions along different specification states are strongly influenced by 3D rearrangement and mechanical properties of the surrounding microenvironment, that can modulate both cell potency and differentiation, through the activation of specific mechanosensing-related pathways. An overview of small molecule ability to modulate cell plasticity and define cell fate is here presented and results, showing the possibility to erase the epigenetic signature of adult dermal fibroblasts and convert them into insulin-producing cells (EpiCC) are described. The beneficial effects exerted on such processes, when cells are homed on an adequate substrate, that shows “in vivo” tissue-like stiffness are also discussed and the contribution of the Hippo signalling mechano-transduction pathway as one of the mechanisms involved is examined. In addition, results obtained using a genetically modified fibroblast cell line, expressing the enhanced green fluorescent protein (eGFP) under the control of the porcine insulin gene (INS) promoter (INS-eGFP transgenic pigs), are reported. This model offers the advantage to monitor the progression of cell conversion in real time mode. All these observations have a main role in order to allow a swift scale-up culture procedure, essential for cell therapy and tissue engineering applied to human regenerative medicine, and fundamental to ensure an efficient translation process from the results obtained at the laboratory bench to the patient bedside. Moreover, the creation of reliable in vitro model represents a key point to ensure the development of more physiological models that, in turn, may reduce the number of animals used, implementing non-invasive investigations and animal welfare and protection.
机译：细胞命运规范，基因表达和空间限制通过表观遗传调控机制进行了微调。同时，已经显示出机械力对于驱动细胞可塑性和促进分化至关重要。确实，一些研究表明，沿不同规格状态的转变受到周围微环境的3D重排和机械性能的强烈影响，可以通过激活特定的机械传感相关途径来调节细胞效能和分化。这里概述了小分子调节细胞可塑性和定义细胞命运的能力，并给出了结果，表明了消除成年真皮成纤维细胞表观遗传特征并将其转化为胰岛素产生细胞（EpiCC）的可能性。还讨论了在将细胞放置在足够的基质上时显示出“体内”组织样硬度的，对此类过程产生的有益作用，并研究了作为相关机制之一的Hippo信号传导途径的作用。此外，还报道了使用基因修饰的成纤维细胞系表达的结果，该细胞系在猪胰岛素基因（INS）启动子的控制下表达增强的绿色荧光蛋白（eGFP）（INS-eGFP转基因猪）。该模型的优点是可以实时监控细胞转化的进程。所有这些观察结果都起着主要作用，以允许进行快速放大培养程序，这对于应用于人类再生医学的细胞疗法和组织工程至关重要，并且从根本上确保了从实验室工作台获得的结果有效翻译的过程。病人床边。此外，建立可靠的体外模型是确保开发更多生理模型的关键，从而可以减少使用的动物数量，实施非侵入性调查以及动物福利和保护。

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