|Jiao Li, Zheng Wang, Qiqi Chu,Kewu Jiang, Juan Li, Nan Tang. The Strength of Mechanical Forces Determines theDifferentiation of Alveolar Epithelial Cells. Developmental Cell. DOI: 10.1016/j.devcel.2018.01.008|
The Strength of Mechanical Forces Determines theDifferentiation of Alveolar Epithelial Cells
Jiao Li, Zheng Wang, Qiqi Chu,Kewu Jiang, Juan Li, Nan Tang
The differentiation of alveolar epithelial type I (AT1)and type II (AT2) cells is essential for the lung gas exchangefunction. Disruption of this process results inneonatal death or in severe lung diseases that lastinto adulthood. We developed live imaging techniquesto characterize the mechanisms that controlalveolar epithelial cell differentiation. We discoveredthat mechanical forces generated from the inhalationof amniotic fluid by fetal breathing movements areessential for AT1 cell differentiation. We found thata large subset of alveolar progenitor cells is able toprotrude from the airway epithelium toward themesenchyme in an FGF10/FGFR2 signaling-dependentmanner. The cell protrusion process resultsin enrichment of myosin in the apical region ofprotruded cells; this myosin prevents these cellsfrom being flattened by mechanical forces, therebyensuring their AT2 cell fate. Our study demonstratesthat mechanical forces and local growth factorssynergistically control alveolar epithelial celldifferentiation.