The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells
The Strength of Mechanical Forces Determines the Differentiation of Alveolar Epithelial Cells
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DOI：
10.1016/j.devcel.2018.01.008
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发表时间：
2018-02-05
影响因子：
11.8
通讯作者：
Tang, Nan
中科院分区：
文献类型：
--
作者：
Li, Jiao;Wang, Zheng;Tang, Nan
肺泡Ⅰ型上皮细胞（AT 1）和Ⅱ型上皮细胞（AT 2）的分化对肺气体交换功能至关重要。这一过程的中断会导致新生儿死亡或持续到成年的严重肺部疾病。我们开发了实时成像技术来表征控制肺泡上皮细胞分化的机制。我们发现，胎儿呼吸运动吸入羊水产生的机械力对AT 1细胞分化至关重要。我们发现，肺泡祖细胞的一个大的子集是能够突出从气道上皮细胞向间充质中的FGF 10/FGFR 2信号依赖的方式。细胞突起过程导致突起细胞顶端区域肌球蛋白富集;该肌球蛋白防止这些细胞被机械力压扁，从而确保其AT 2细胞命运。我们的研究表明，机械力和局部生长因子协同控制肺泡上皮细胞分化。
The differentiation of alveolar epithelial type I (AT1) and type II (AT2) cells is essential for the lung gas exchange function. Disruption of this process results in neonatal death or in severe lung diseases that last into adulthood. We developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. We discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for AT1 cell differentiation. We found that a large subset of alveolar progenitor cells is able to protrude from the airway epithelium toward the mesenchyme in an FGF10/FGFR2 signaling-dependent manner. The cell protrusion process results in enrichment of myosin in the apical region of protruded cells; this myosin prevents these cells from being flattened by mechanical forces, thereby ensuring their AT2 cell fate. Our study demonstrates that mechanical forces and local growth factors synergistically control alveolar epithelial cell differentiation.