Department of Biology, University of Texas at Arlington, Arlington, TX, USA.
Advanced Technology Cores, Baylor College of Medicine, Houston, TX, USA.
BMC Genomics. 2022 Jan 4;23(1):6. doi: 10.1186/s12864-021-08226-5.
Snakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities.
Here, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response.
Collectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.
蛇在经历数月的禁食后，其肠道会进行极端的再生，这涉及代谢、功能和组织生长的空前增加，但这一过程的具体分子控制尚不清楚。了解协调这些再生表型的机制为理解可能控制脊椎动物再生的关键途径以及脊椎动物再生能力的新视角提供了有价值的机会。
在这里，我们整合了来自蟒蛇的一组全面的表型、转录组、蛋白质组和磷酸化蛋白质组数据，以确定协调代谢、营养吸收和细胞应激转变的机制，从而指导再生反应的各个阶段。我们确定了代谢、应激反应和生长途径激活的特定时间模式，这些模式指导着再生，并为整合这些信号的多个关键中央调节分子激酶提供了证据，包括 mTOR 信号和未折叠蛋白反应等主要保守途径。
总的来说，我们的结果确定了应激反应在肠道再生中的一种新的开关样作用，它形成了一个主要的调节枢纽，促进器官再生，并可能为理解脊椎动物的再生能力指明潜在途径。
