LSC 2013 abstract - Differentiated type II pneumocytes can be reprogrammed by ectopic Sox2 expression

The lung is an essential organ required for gas exchange in all air-breathing animals. Development of the lungs starts when the foregut forms an endodermal bud, which invaginates the surrounding mesenchyme and subsequently branches to form the bronchial tree. Sox2 is an evolutionarily conserved transcription factor important for development of several organs. Previously, we showed that Sox2 plays critical roles in branching morphogenesis and in the determination of epithelial cell fate. In order to investigate the role of Sox2 in the reprogramming of mature epithelial cells, we the bi-transgenic approach to ectopically expressed Sox2 in terminally differentiated type II pneumocytes of adult mouse lungs. This resulted in emphysematous lungs and aberrant structures containing cuboidal cells in the periphery of the lungs. These cuboidal cells expressed the transgenic Sox2 protein, as well as markers specific for proximal epithelium, such as Ccsp. This indicates that the fully differentiated distal, Spc-positive alveolar epithelial cells changed their phenotype towards proximal, Ccsp positive cells. Moreover, short term expression of the Sox2 transgene showed that the type II cells first co-expressed proSPC and Ccsp, like embryonic lung epithelial cells, as well as a specific progenitor marker, Sca-1. Next, the cells become proliferative and start to differentiate into cuboidal cells, indicating that fully differentiated type II cells can be reprogrammed with Sox2 to develop a proximal phenotype. Thus, our results suggest that fully differentiated alveolar type II cells can be reprogrammed in vivo by Sox2.