Emmons-Bell Maya, Durant Fallon, Tung Angela, Pietak Alexis, Miller Kelsie, Kane Anna, Martyniuk Christopher J, Davidian Devon, Morokuma Junji, Levin Michael
Allen Discovery Center at Tufts University, Medford, MA 02155, USA; Department of Biology, Tufts University, Medford, MA 02155, USA.
Allen Discovery Center at Tufts University, Medford, MA 02155, USA.
iScience. 2019 Dec 20;22:147-165. doi: 10.1016/j.isci.2019.11.014. Epub 2019 Nov 9.
Anatomical homeostasis results from dynamic interactions between gene expression, physiology, and the external environment. Owing to its complexity, this cellular and organism-level phenotypic plasticity is still poorly understood. We establish planarian regeneration as a model for acquired tolerance to environments that alter endogenous physiology. Exposure to barium chloride (BaCl) results in a rapid degeneration of anterior tissue in Dugesia japonica. Remarkably, continued exposure to fresh solution of BaCl results in regeneration of heads that are insensitive to BaCl. RNA-seq revealed transcriptional changes in BaCl-adapted heads that suggests a model of adaptation to excitotoxicity. Loss-of-function experiments confirmed several predictions: blockage of chloride and calcium channels allowed heads to survive initial BaCl exposure, inducing adaptation without prior exposure, whereas blockade of TRPM channels reversed adaptation. Such highly adaptive plasticity may represent an attractive target for biomedical strategies in a wide range of applications beyond its immediate relevance to excitotoxicity preconditioning.
解剖学稳态源于基因表达、生理学和外部环境之间的动态相互作用。由于其复杂性，这种细胞和生物体水平的表型可塑性仍未得到充分理解。我们将涡虫再生确立为一种对改变内源性生理的环境获得耐受性的模型。暴露于氯化钡（BaCl）会导致日本三角涡虫前部组织迅速退化。值得注意的是，持续暴露于新鲜的BaCl溶液会导致对BaCl不敏感的头部再生。RNA测序揭示了适应BaCl的头部的转录变化，这提示了一种对兴奋性毒性的适应模型。功能丧失实验证实了几个预测：阻断氯离子和钙通道可使头部在最初暴露于BaCl时存活下来，在没有预先暴露的情况下诱导适应，而阻断TRPM通道则会逆转适应。这种高度适应性的可塑性可能代表了生物医学策略在广泛应用中的一个有吸引力的靶点，其意义远不止于与兴奋性毒性预处理的直接关联。
