Regulation of the Alveolar Epithelial Transitional State in Murine and Human Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring disease arising from impaired regeneration of the alveolar epithelium after injury. During regeneration, type 2 alveolar epithelial cells (AEC2s) differentiate into AEC1s via a transitional state that upregulates keratin 8. In IPF, transitional AECs persist with ineffectual AEC1 differentiation. However, whether keratin 8 regulates transitional state persistence and fibrosis is unclear. Here, we isolated AEC2s from WT or keratin 8 KO mice and harvested RNA from freshly isolated cells or from cells cultured for 1, 3, or 7 days. RNAseq was performed. AEC2s were isolated from WT or KO mice. RNA was harvested from freshly isolated cells (Day 0 or D0). Cells were cultured, and RNA was harvested at Day 1, 3, and 7 (D1, D3, D7). This was done 3 times, on 6/17/2021, 7/14/2021, and 8/3/2021, for 3 independent biological replicates. RNAseq was performed.