Rost Fabian, Rodrigo Albors Aida, Mazurov Vladimir, Brusch Lutz, Deutsch Andreas, Tanaka Elly M, Chara Osvaldo
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.
Elife. 2016 Nov 25;5:e20357. doi: 10.7554/eLife.20357.
Axolotls are unique in their ability to regenerate the spinal cord. However, the mechanisms that underlie this phenomenon remain poorly understood. Previously, we showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we refine the analysis of cell proliferation in space and time and identify a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time. By tracking sparsely-labeled cells, we also quantify cell influx into the regenerate. Taking a mathematical modeling approach, we integrate these quantitative datasets of cell proliferation, neural stem cell activation and cell influx, to predict regenerative tissue outgrowth. Our model shows that while cell influx and neural stem cell activation play a minor role, the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls.
美西螈在脊髓再生能力方面独具特色。然而，这一现象背后的机制仍知之甚少。此前，我们发现美西螈脊髓中的再生干细胞会恢复到类似于胚胎神经上皮细胞的分子状态，并在功能上获得快速增殖分裂能力（罗德里戈·阿尔博斯等人，2015年）。在此，我们优化了对细胞增殖在空间和时间上的分析，并在再生脊髓中确定了一个高增殖区，该区域会随着时间向后移动。通过追踪稀疏标记的细胞，我们还对进入再生组织的细胞流入量进行了量化。采用数学建模方法，我们整合了这些关于细胞增殖、神经干细胞激活和细胞流入的定量数据集，以预测再生组织的生长。我们的模型表明，虽然细胞流入和神经干细胞激活作用较小，但细胞周期的加速是美西螈再生脊髓生长的主要驱动因素。
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