Poster #023, Stanford University
Characterizing Primary Cilia in AT2 Cells During Lung Injury
Mentors: Csenge Rezi, PhD and Peter Jackson, PhD
Alveolar type II (AT2) cells are the primary stem cells of the lungs and play a critical role in tissue repair by differentiating into Alveolar type I (AT1) cells following injury. In idiopathic pulmonary fibrosis (IPF), a chronic lung disease that causes irreversible scarring of the lung tissue that impairs gas exchange, it is thought that the dysfunction of AT2 cell signaling leads to the development of fibrosis.
Primary cilia are small organelles that act as a hub for different signaling pathways. Aberrant ciliary signaling after injury has been shown to promote fibrosis in other organs, such as the kidney. However, the presence and role of primary cilia during lung injury remain poorly understood. Previous research found that there is an increase of primary cilia in IPF lungs, yet how ciliation is regulated across the injury-repair trajectory remains unknown. The objective of the project was to determine if AT2 cells possess primary cilia, and if cilia regulate AT2 cell signaling.
Our methodology involved performing immunofluorescence microscopy on mouse lung collected at D0, D7, D12, and D30 after bleomycin-induced injury by a collaborating lab, and we immunostained for AT2 cells and primary cilia over the injury-repair timeline.
We observed that the number of primary cilia increased at D7 following injury before declining during later stages. At the peak of injury, primary cilia were also longer, and some AT2 cells possessed primary cilia. However, cilia were predominantly localized to cells adjacent to AT2 cells. These findings suggest that primary cilia are dynamically regulated during lung injury, and that other cell types with primary cilia may play a greater role in the injury response than AT2 cell cilia. These results provide a foundation for future studies investigating how cilia regulate signaling to or from the AT2 cells and how it contributes to IPF.