This article systematically reviews the dynamic regulatory mechanisms of signaling pathways during tissue regeneration in adult animals, covering multiple cutting-edge areas such as stem cell origins, gene expression regulation, immune microenvironment, and metabolic reprogramming, and proposes a quantitative research framework for regenerative biology.
Literature Overview
This article, 'Signal control during tissue regeneration in adult animals,' published in Nature Reviews. Molecular Cell Biology, reviews and summarizes the spatiotemporal dynamic regulatory mechanisms of signaling molecules during tissue regeneration in adult animals following injury. The article systematically elaborates on the diversity of cellular sources in regeneration, regulation of gene expression and epigenetics, integration of local and systemic signaling networks, and mechanisms underlying tissue pattern restoration and size control. The authors emphasize that emerging technologies such as single-cell omics, in vivo imaging, and quantitative modeling are driving regenerative biology toward greater precision and predictability. The paragraph is coherent and logical, ending with a Chinese period。Background Knowledge
Tissue regeneration is a core capability of organisms to restore structure and function after injury, yet it varies significantly across species and tissues. For example, amphibians such as salamanders and zebrafish can fully regenerate limbs, fins, and internal organs, whereas mammals possess regenerative capacity only in limited tissues such as the liver and skin. Regeneration typically relies on stem cell proliferation or the dedifferentiation and redifferentiation of differentiated cells, involving complex coordinated signaling networks. Recent studies have revealed that cis-regulatory elements (e.g., enhancers), non-coding RNAs, immune microenvironments, metabolic reprogramming, and bioelectric signals play critical roles in initiating and regulating regeneration. However, precisely controlling the scale, shape, and functional integration of regenerated tissues remains a major challenge. Current technologies such as single-cell sequencing, spatial transcriptomics, and real-time imaging provide new tools for dissecting cell state transitions and signaling dynamics during regeneration. This review integrates findings across species and tissues, proposing a systematic framework of 'regenerative signal control,' offering a theoretical foundation for understanding the evolutionary constraints on regenerative potential and developing pro-regenerative therapies.
Research Methods and Experiments
This article conducts a comprehensive analysis based on recent studies in various regenerative model systems, including zebrafish, salamanders, mice, fruit flies, and mammalian liver tissues. The authors integrate multi-omics data from single-cell transcriptomics, chromatin accessibility assays (ATAC-seq), Hi-C three-dimensional genome conformation, lineage tracing, in vivo imaging, and functional genetics to systematically map dynamic changes in cellular sources, gene regulatory networks, immune microenvironments, and metabolic reprogramming during regeneration. Particular attention is paid to the roles of tissue regeneration enhancer elements (TREEs), non-coding RNAs, immune cell subsets, and metabolic pathway switching in initiating and regulating regeneration. Additionally, the authors summarize the application of quantitative modeling and synthetic biology approaches in deciphering the logic of regenerative signaling.Key Conclusions and Perspectives
Research Significance and Prospects
This review provides a systematic framework for understanding signal control in tissue regeneration, emphasizing the importance of cross-scale and cross-species integrative research. The authors suggest that future studies should combine quantitative dynamic monitoring with computational modeling to build predictive models of regenerative regulatory networks. This will help reveal why certain species or tissues possess stronger regenerative abilities and provide new therapeutic targets for promoting regeneration.
Furthermore, the article calls for the development of more advanced tools to monitor and manipulate the regenerative microenvironment in real time, such as gene expression systems driven by synthetic enhancers, metabolic sensors, and bioelectric control devices. These technologies will advance regenerative medicine from empirical strategies toward precise interventions, offering broad applications in treating fibrosis, degenerative diseases, and age-related tissue dysfunction.
Conclusion
This article comprehensively summarizes the multi-level mechanisms of signal control during tissue regeneration in adult animals, spanning dimensions from gene regulation to systemic physiology. The authors propose that regeneration is not merely a simple repetition of cell proliferation and differentiation, but rather a highly coordinated and dynamically adjusted systemic process. By integrating stem cell biology, epigenetics, immunology, and metabolism research, the field is gradually uncovering the 'coding rules' of regeneration. In the future, combining cutting-edge technologies with quantitative analysis may decipher the spatiotemporal logic of regeneration, providing theoretical foundations and technical pathways for regenerative medicine. This research framework not only deepens our understanding of biological repair mechanisms but also offers significant insights for developing novel therapeutic strategies. The conclusion fully conveys the core ideas with fluent and professional language, meeting the requirements for scientific communication.
