RNA-Seq reveals different mRNA abundance of transporters and their alternative transcript isoforms during liver...

During development, the maturation of liver transporters is essential for chemical elimination in newborns and children. One cannot compare the real abundance of transcripts by conventional messenger RNA (mRNA) profiling methods; in comparison, RNA-Seq provides a "true quantification" of transcript counts and an unbiased detection of novel transcripts. The purpose of this study was to compare the mRNA abundance of liver transporters and seek their novel transcripts during liver development. Livers from male C57BL/6J mice were collected at 12 ages from prenatal to adulthood. The transcriptome was determined by RNA-Seq, with transcript abundance estimated by Cufflinks. Among 498 known transporters, the ontogeny of 62 known critical xenobiotic transporters was examined in detail. The cumulative mRNAs of the uptake transporters increased more than the efflux transporters in livers after birth. A heatmap revealed three ontogenic patterns of these transporters, namely perinatal (reaching maximal expression before birth), adolescent (about 20 days), and adult enriched (about 60 days of age). Before birth, equilibrative nucleoside transporter 1 was the transporter with highest expression in liver (29%), followed by breast cancer resistance protein (Bcrp) (26%). Within 1 day after birth, the mRNAs of these two transporters decreased markedly, and Ntcp became the transporter with highest expression (52%). In adult liver, the transporters with highest expression were organic cation transporter 1 and Ntcp (23% and 22%, respectively). Three isoforms of Bcrp with alternate leading exons were identified (E1a, E1b, and E1c), with E1b being the major isoform. In conclusion, this study reveals the mRNA abundance of transporters in liver and demonstrates that the expression of liver transporters is both age and isoform specific.