1. Deformation-induced transitional myofibroblasts contribute to compensatory lung growth
- Author
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Saumyadipta Pyne, Jonna Grimsby, Steven J. Mentzer, Alexandra B. Ysasi, Willi L. Wagner, Maximilian Ackermann, Paul C. Blainey, Cristian D. Valenzuela, Shuqiang Li, Kenneth J. Livak, Prapti Pokharel, Akira Tsuda, Robert D. Bennett, Massachusetts Institute of Technology. Department of Biological Engineering, and Blainey, Paul C
- Subjects
Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Transcription, Genetic ,Physiology ,medicine.medical_treatment ,Compensatory growth (organ) ,Cell Separation ,Deformation (meteorology) ,Biology ,Polymerase Chain Reaction ,03 medical and health sciences ,Pneumonectomy ,Physiology (medical) ,medicine ,Animals ,Myofibroblasts ,Lung ,Image Cytometry ,Gene Expression Regulation, Developmental ,Cell Biology ,respiratory system ,Actins ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Stress, Mechanical ,Single-Cell Analysis ,Myofibroblast ,Research Article - Abstract
In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented by plombage or phrenic nerve transection (P < 0.001). Within 3 days of pneumonectomy, the frequency of SMA⁺ cells in subpleural alveolar ducts was significantly increased (P < 0.01). To determine the functional activity of these SMA⁺ cells, we isolated regenerating alveolar ducts by laser microdissection and analyzed individual cells using microfluidic single-cell quantitative PCR. Single cells expressing the SMA (Acta2) gene demonstrated significantly greater transcriptional activity than endothelial cells or other discrete cell populations in the alveolar duct (P < 0.05). The transcriptional activity of the Acta2⁺ cells, including expression of TGF signaling as well as repair-related genes, suggests that these myofibroblast-like cells contribute to compensatory lung growth. Keywords: compensatory growth; gene expression; lung; myofibroblasts, National Institutes of Health (U.S.) (Grant HL94567), National Institutes of Health (U.S.) (Grant CA009535), National Institutes of Health (U.S.) (Grant ES000002)
- Published
- 2017