GSE122919
Lin28 expression affect embryonic lung development
Lin28A and its paralog Lin28B are RNA binding proteins that regulate gene expression by inhibition of the maturation of the Per/Pri Let-7 miRNAs family and also via Let-7 independent mechanism. To study the effect of Lin28A ectopic-expression on mouse embryonic development we used a transgenic mice strain that combine a Cre-Lox system and a Tet-On system (herein Lox-stop-Lox-TetOn-Lin28A mice) and enable spatial and temporal control of transgenic Lin28A over-expression. Here we show that global Lin28A over-expression (by crossing Lox-stop-Lox-TetOn-Lin28A males with VasaCre females) in the mouse embryo prevents embryonic lung development. To study the precise developmental stage affected by Lin28A expression we preformed RNA sequencing analysis for transgenic and control lungs from E12.5, E14.5, E16.5 and E18.5 embryos. This analysis revealed that the development of the lung was delayed but not completely abrogated by Lin28A expression. We further showed that the effect of Lin28A expression in the mesenchymal cells (by crossing Lox-stop-Lox-TetOn-Lin28A males with Wt1Cre females)  of the lung leads to the same phenotype as global Lin28A expression while expression in the lung epithelial cells (by crossing the Lox-stop-Lox-TetOn-Lin28A males with Nkx2.1Cre females) result in a milder developmental phenotype. Overall design: RNA seq analysis was preformed for the following samples in triplicate (unless otherwise indicated): E12.5, E14.5, E16.5, E18.5 (5 repeats) control lungs. E12.5, E14.5 (4 repeats), E16.5, E18.5 (5 repeats) transgenic lungs derived from embryos with global Lin28A overexpression. E18.5 transgenic lungs derived from embryos with specific Lin28A expression in the lung epithelial cells. E18.5 transgenic lungs derived from embryos with Lin28A expression in the lung mesenchymal cells (duplicate).