Presentation Type
Poster Presentation
Abstract
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) characterized by excessive extracellular matrix (ECM) deposition. The prognosis of IPF is poor, with the only curative option for the disease being lung transplantation. Prior studies have described increased expression of the lncRNA Meg3 in the lungs of IPF patients. Increased expression of Meg3 is associated with impaired lung repair through inhibition of lung basal progenitor cell differentiation. In this study, the lung alveolar epithelium was investigated in murine models of IPF and organoid culture. Lineage tracing and immunofluorescence confocal microscopy techniques were employed to identify the cell fate of type 2 alveolar epithelial cells (AT2), the stem cell of the alveolar epithelium, and restoration of type 1 alveolar epithelial cells (AT1) that conduct gas exchange. Previous work identified abnormal differentiation of AT2 cells into airway-like epithelial cells associated with failed repair in IPF, and we therefore assessed airway cell markers in these lineage traced cells. Meg3 knockout lineage-traced AT2s showed decreases in expression of AT2, AT1, or transitional cell markers following injury with bleomycin. These data indicate a decrease in AT2 to AT1 transition following Meg3 knockout, resulting in a loss of normal alveolar repair. To determine the role of increased Meg3 in the IPF lung, Meg3 was expressed in human AT2 cell cultures. RealTime-qPCR data revealed that expressing Meg3 induced p53, a known Meg3 target, as well as Cebpa, a gene associated with maintenance of AT2 cells, while reducing Scgb3a2, a gene associated with airway secretory epithelial cells.
Faculty Mentor
Jason J. Gokey, Vanderbilt University Medical Center
Recommended Citation
Colvard, Arlo; DiGiovanni, Gianluca; Gaona, Isabella; Gutor, Sergey S.; Singha, Ujjal; Sherrill, Taylor P.; Nichols, David S.; Zhou, Yunli; Kropski, Jonathan A.; and Gokey, Jason J., "The Loss of Meg3 Causes Abnormal Alveolar Epithelial Progenitor Cell Differentiation" (2025). Student Scholar Symposium. 9.
https://digitalcollections.lipscomb.edu/student_scholars_symposium/2025/Full_schedule/9
Included in
The Loss of Meg3 Causes Abnormal Alveolar Epithelial Progenitor Cell Differentiation
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) characterized by excessive extracellular matrix (ECM) deposition. The prognosis of IPF is poor, with the only curative option for the disease being lung transplantation. Prior studies have described increased expression of the lncRNA Meg3 in the lungs of IPF patients. Increased expression of Meg3 is associated with impaired lung repair through inhibition of lung basal progenitor cell differentiation. In this study, the lung alveolar epithelium was investigated in murine models of IPF and organoid culture. Lineage tracing and immunofluorescence confocal microscopy techniques were employed to identify the cell fate of type 2 alveolar epithelial cells (AT2), the stem cell of the alveolar epithelium, and restoration of type 1 alveolar epithelial cells (AT1) that conduct gas exchange. Previous work identified abnormal differentiation of AT2 cells into airway-like epithelial cells associated with failed repair in IPF, and we therefore assessed airway cell markers in these lineage traced cells. Meg3 knockout lineage-traced AT2s showed decreases in expression of AT2, AT1, or transitional cell markers following injury with bleomycin. These data indicate a decrease in AT2 to AT1 transition following Meg3 knockout, resulting in a loss of normal alveolar repair. To determine the role of increased Meg3 in the IPF lung, Meg3 was expressed in human AT2 cell cultures. RealTime-qPCR data revealed that expressing Meg3 induced p53, a known Meg3 target, as well as Cebpa, a gene associated with maintenance of AT2 cells, while reducing Scgb3a2, a gene associated with airway secretory epithelial cells.