Javier Arcos Hodar,Sascha Jung,Mohamed Soudy,Sybille Barvaux,Antonio Del Sol
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引用次数: 0
摘要
目前的年轻化策略,从卡路里限制到体内部分重编程,都只能改善一些特定的细胞过程。此外,这些方法背后的分子机制大多不为人知,这阻碍了更全面的细胞年轻化策略的设计。为了解决这个问题,我们开发了细胞年轻化图谱 SINGULAR(Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity),以单细胞分辨率对多个器官的多种年轻化策略进行统一的系统生物学分析。特别是,我们利用网络生物学方法,在细胞内信号传导、细胞间通讯和转录调控水平上描述和比较了每种策略的效果。结果,我们发现了协调年轻化反应的主调节因子,并提出以这些调节因子的组合为靶点,可以更全面地改善年龄失调的细胞过程。因此,与 SINGULAR 配套的互动数据库有望促进未来合成年轻化干预措施的设计。
The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies.
Current rejuvenation strategies, which range from calorie restriction to in vivo partial reprogramming, only improve a few specific cellular processes. In addition, the molecular mechanisms underlying these approaches are largely unknown, which hinders the design of more holistic cellular rejuvenation strategies. To address this issue, we developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity), a cell rejuvenation atlas that provides a unified system biology analysis of diverse rejuvenation strategies across multiple organs at single-cell resolution. In particular, we leverage network biology approaches to characterize and compare the effects of each strategy at the level of intracellular signaling, cell-cell communication, and transcriptional regulation. As a result, we identified master regulators orchestrating the rejuvenation response and propose that targeting a combination of them leads to a more holistic improvement of age-dysregulated cellular processes. Thus, the interactive database accompanying SINGULAR is expected to facilitate the future design of synthetic rejuvenation interventions.