GSE111569
Etv5 ChIP-seq in AT2 cells
Alveolar type II (AT2) cell dysfunction contributes to a number of  significant human pathologies including respiratory distress syndrome,  lung adenocarcinoma, and debilitating fibrotic diseases,  but the critical transcription factors that maintain AT2 cell identity  are unknown. Here we show that the E26 transformation-specific  (ETS) family transcription factor Etv5 is essential tomaintain AT2 cell  identity. Deletion of Etv5 from AT2 cells produced gene and protein  signatures characteristic of differentiated alveolar type I (AT1) cells.  Consistent with a defect in the AT2 stem cell population, Etv5 deficiency  markedly reduced recovery following bleomycin-induced  lung injury. Lung tumorigenesis driven by mutant KrasG12D was  also compromised by Etv5 deficiency. ERK activation downstream  of Ras was found to stabilize Etv5 through inactivation of the cullin-  RING ubiquitin ligase CRL4COP1/DET1 that targets Etv5 for proteasomal  degradation. These findings identify Etv5 as a critical output of  Ras signaling in AT2 cells, contributing to both lung homeostasis and tumor initiation. Overall design: AT2 cells (2 X 10^7) were isolated from 10- to 12-wk-old  C57BL/6 mice. Active Motif Epigenetic Services performed  ChIP assays.