King Benjamin L, Rosenstein Michael C, Smith Ashley M, Dykeman Christina A, Smith Grace A, Yin Viravuth P
1Kathryn Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672 USA.
2Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469 USA.
NPJ Regen Med. 2018 May 29;3:10. doi: 10.1038/s41536-018-0049-0. eCollection 2018.
Regeneration is an endogenous process of tissue repair that culminates in complete restoration of tissue and organ function. While regenerative capacity in mammals is limited to select tissues, lower vertebrates like zebrafish and salamanders are endowed with the capacity to regenerate entire limbs and most adult tissues, including heart muscle. Numerous profiling studies have been conducted using these research models in an effort to identify the genetic circuits that accompany tissue regeneration. Most of these studies, however, are confined to an individual injury model and/or research organism and focused primarily on protein encoding transcripts. Here we describe RegenDbase, a new database with the functionality to compare and contrast gene regulatory pathways within and across tissues and research models. RegenDbase combines pipelines that integrate analysis of noncoding RNAs in combination with protein encoding transcripts. We created RegenDbase with a newly generated comprehensive dataset for adult zebrafish heart regeneration combined with existing microarray and RNA-sequencing studies on multiple injured tissues. In this current release, we detail microRNA-mRNA regulatory circuits and the biological processes these interactions control during the early stages of heart regeneration. Moreover, we identify known and putative novel lncRNAs and identify their potential target genes based on proximity searches. We postulate that these candidate factors underscore robust regenerative capacity in lower vertebrates. RegenDbase provides a systems-level analysis of tissue regeneration genetic circuits across injury and animal models and addresses the growing need to understand how noncoding RNAs influence these changes in gene expression.
再生是一种组织修复的内源性过程，最终可实现组织和器官功能的完全恢复。虽然哺乳动物的再生能力仅限于特定组织，但像斑马鱼和蝾螈这样的低等脊椎动物具有再生整个肢体以及包括心肌在内的大多数成年组织的能力。为了识别伴随组织再生的基因回路，人们使用这些研究模型进行了大量的分析研究。然而，这些研究大多局限于单个损伤模型和/或研究生物体，并且主要集中在蛋白质编码转录本上。在此，我们描述了RegenDbase，这是一个新的数据库，具有比较和对比不同组织和研究模型内部及之间基因调控途径的功能。RegenDbase整合了对非编码RNA与蛋白质编码转录本进行分析的流程。我们利用新生成的成年斑马鱼心脏再生综合数据集，结合现有的关于多种损伤组织的微阵列和RNA测序研究，创建了RegenDbase。在当前版本中，我们详细阐述了微小RNA - mRNA调控回路以及这些相互作用在心脏再生早期阶段所控制的生物学过程。此外，我们识别出已知的和假定的新型长链非编码RNA，并基于邻近搜索确定它们的潜在靶基因。我们推测这些候选因子突出了低等脊椎动物强大的再生能力。RegenDbase提供了跨损伤和动物模型的组织再生基因回路的系统级分析，并满足了人们日益增长的对于理解非编码RNA如何影响基因表达变化的需求。
