Differential expression of natural antisense transcripts during liver development in embryonic mice

The mature adult liver is a metabolizing and synthesizing organ consisting of hepatic lobules. The liver development during fetal stages is induced by the interaction between hepatoblast cells derived from the endoderm and stellate cells and/or endothelial cells derived from the mesoderm. Recently, the association of non-coding RNAs, such as microRNAs, in the liver development process has been reported. In the present study, the gene expression changes were investigated of natural antisense transcripts (NATs), a type of non-coding RNA, during the liver development using livers from embryonic day (E) 14, E17, E19 and newborn (NB). The upregulated NATs of 87 genes and the downregulated NATs of 26 genes were identified when the expression was >5.0-fold up/downregulated NATs at E17, E19 or NB compared to those at E14, as examined by microarray analysis. Among these NATs, strand-specific reverse transcription-quantitative polymerase chain reaction analyses validated that the NAT expression of Fga, Fgb, Fgg, F2, Apoa1, Fabp1, C3 and Proc, which have metabolic and synthesizing functions in the adult liver, increased, whereas the NAT expression of Ermap and Tfrc, which function in the hematopoiesis, decreased during the developmental stages. These results indicate that the differential expression of several NATs is induced during the process of liver development, suggesting that these NATs may be involved in the regulation of gene expression and functional conversion from a hematopoietic to a metabolic organ in the developmental stages of the liver.