Cheung Stephanie, Bredikhin Danila, Gerber Tobias, Steenbergen Petrus J, Basu Soham, Bailleul Richard, Hansen Pauline, Paix Alexandre, Benton Matthew A, Korswagen Hendrik C, Arendt Detlev, Stegle Oliver, Ikmi Aissam
European Molecular Biology Laboratory (EMBL), Developmental Biology Unit, Heidelberg 69117, Germany.
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg 69117, Germany; Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Dev Cell. 2025 Mar 10;60(5):780-793.e7. doi: 10.1016/j.devcel.2024.11.001. Epub 2024 Nov 29.
The complexity of regeneration extends beyond local wound responses, eliciting systemic processes across the entire organism. However, the functional relevance and coordination of distant molecular processes remain unclear. In the cnidarian Nematostella vectensis, we show that local regeneration triggers a systemic homeostatic response, leading to coordinated whole-body remodeling. Leveraging spatial transcriptomics, endogenous protein tagging, and live imaging, we comprehensively dissect this systemic response at the organismal scale. We identify proteolysis as a critical process driven by both local and systemic upregulation of metalloproteases. We show that metalloproteinase expression levels and activity scale with the extent of tissue loss. This proportional response drives long-range tissue and extracellular matrix movement. Our findings demonstrate the adaptive nature of the systematic response in regeneration, enabling the organism to maintain shape homeostasis while coping with a wide range of injuries.
再生的复杂性不仅限于局部伤口反应，还引发了整个生物体的系统性过程。然而，远距离分子过程的功能相关性和协调性仍不清楚。在刺胞动物星状海葵中，我们发现局部再生会触发系统性稳态反应，导致全身协调重塑。利用空间转录组学、内源性蛋白质标记和活体成像技术，我们在生物体尺度上全面剖析了这种系统性反应。我们确定蛋白水解是由金属蛋白酶的局部和系统性上调驱动的关键过程。我们表明，金属蛋白酶的表达水平和活性与组织损失程度成比例。这种比例反应驱动远距离组织和细胞外基质的移动。我们的研究结果证明了再生中系统性反应的适应性本质，使生物体在应对各种损伤时能够维持形态稳态。
