Expanded transcriptomic analysis of human hepatic stellate cells links novel coding and noncoding products to human liver fibrosis

We have performed analysis of the transcriptome of human HSCs to define the long noncoding (lnc) RNAs expressed in this cell type, including many not previously annotated. Through analysis of full-length RNA transcripts, we identified additional lncRNAs that were not assembled by short reads. We also discovered new isoforms of protein coding genes that encode amino acid sequences that are not present in annotated isoforms. Analysis of non-polyadenylated RNAs did not identify additional genes encoding long noncoding RNA transcripts, but did reveal the presence of hundreds of circular (circ) RNAs, including those with potential for translation. Incorporating these transcripts and genes into analysis of a published dataset of human liver fibrosis revealed the induction of lncRNAs, novel protein isoforms, and circRNAs associated with development of disease. These results identify RNAs and amino acid sequences expressed in HSCs and associated with human liver disease that may serve as therapeutic targets to inhibit fibrosis or biomarkers to benchmark progression of disease.