RNA-seq analyses of mouse embryonic fibloblasts (MEFs) reprogrammed into induced pulmonary epithelial cell-like cells

RNA-seq analyses of MEFs obtained from GFP/SP-C transgenic mice on CBA/Ca x C57BL/6 mixed background were transduced sets of 3 or 4 combination factors (Nkx2-1/Foxa1/Gata, Nkx2-1/Foxa2/Gata, Nkx2-1/Foxa1/Foxa2/Gata6) into induced pulmonary epithelial cell-like cells 14 days after the transduction. Abstract is as follows: pneumocyte differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells. However, direct reprograming of somatic cells into pulmonary epithelial cells has not been achieved. Here, we report that a combination of three or four transcription factors (i.e., Nkx2-1, Gata6, and [Foxa1 and/or Foxa2]) directly reprogrammed mouse tail-tip fibroblast or embryonic fibroblast into differentiated induced pulmonary epithelial cell-like cells (iPUL cells). iPUL cells had a global gene expression profile similar to various kinds of pulmonary epithelial cells. Some iPUL cells showed lamellar body-like structures and expressed SP-C, consistent with the features of alveolar epithelial type II cells. Interestingly, intratracheal administration of iPUL cells rescued influenza virus-induced acute lung injury in mice. These findings demonstrate that functional pulmonary epithelial cell-like cells can be directly reprogrammed from differentiated somatic cells by defined factors. Reprograming of fibroblasts might provide a source of pulmonary epithelial cells for regenerative medicine. Publicly available raw RNA-seq data (GSE80101) representing whole mouse lung (SRR3353494, SRR3353497, SRR3353498) and alveolar type II cells (SRR3353495, SRR3353500, SRR3353510, SRR3353512) sorted in the basis of EpCAM+ and dTomato+ from SpcCreERT2;RosatdTomato mice were also simultaneously processed with our data. Overall design: RNA-seq: 12 samples