PLX301819

GSE140071: Genome-wide integration of microRNA and the transcriptome during human alveolar epithelial cell transdifferentiation identifies SGK1 as novel target of miR-424/503 [RNA-Seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The alveolar epithelium is comprised of two cell types, alveolar type 1 (AT1) and type 2 (AT2) cells, the latter being capable of self-renewal and transdifferentiation into AT1 fate to establish alveolar function. Micro-RNAs (miRNAs) re critical regulators of developmental pathways, including branching morphogenesis. To determine if miRNAs also play a crucial role in establishment/maintenance of cellular identity within the alveolar epithelium, we performed genome-wide analysis of miRNAs alongside transcriptomic alterations during transdifferentiation of human AT2 (hAT2) into AT1-like cells in vitro. Our results indicated that miRNAs are tightly correlated to known gene expression pattern changes during AEC differentiation. We were able to define three phases of miRNA expression during the transdifferentiation process, early, late and consistently changed, which further sub-classified as up- or downregulated. miRNAs with altered expression at all time points during AT1-like differentiation were the largest subgroup, suggesting the need for consistent regulation of signaling pathways to mediate transdifferentiation. Target prediction analysis and integration with previously published gene expression data identified glucocorticoid signaling as the top pathway regulated by miRNAs. Serum/glucocorticoid kinase 1 (SGK1) emerged as a central regulatory factor with temporally-correlated loss of expression and gain of hsa-miR-424 and hsa-miR-503 expression. Functional validation demonstrated specific targeting of these miRNAs to the 3UTR of SGK1. Taken together, our data show the time-related contribution of miRNAs to the alveolar transdifferentiation process and suggest the need for inhibition of glucocorticoid pathway signaling to achieve the AT1-like cell phenotype in vitro. The miRNA-mRNA interactions identified herein may help to establish AT2 to AT1 cell differentiation in vivo. SOURCE: Crystal,N,MarconettCrystal Marconett University of Southern California