Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK.
Developmental Biology Unit and Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Mol Syst Biol. 2018 Aug 29;14(8):e8174. doi: 10.15252/msb.20178174.
Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.
鼠类真皮中含有功能和空间上不同的成纤维细胞谱系，这些谱系在出生后早期停止增殖。在这里，我们提出了一个模型，即细胞外基质（ECM）沉积和成纤维细胞增殖之间的负反馈环决定了真皮结构。我们模型的虚拟组织模拟忠实地再现了真皮成熟，预测了成纤维细胞谱系空间分离的丧失，并表明成纤维细胞迁移仅需要用于伤口愈合。为了验证这一点，我们对真皮成纤维细胞进行了实时成像，结果表明，组织的稳态结构是在没有细胞主动迁移的情况下实现的。相比之下，成纤维细胞增殖和迁移都是创伤后组织修复的关键决定因素。研究结果表明，组织尺度的协调是由细胞增殖和 ECM 沉积的相互依赖性驱动的，为确定新的治疗策略以增强皮肤再生铺平了道路。
