Figure 5

Livers from mtm zebrafish exhibit widespread transcriptional changes.

Comparative RNA-Seq from isolated livers from 7 dpf larvae from the following conditions: WT, mtm mutants, WT exposed to a high-fat diet (overfed), WT exposed to alcohol (EtOH-treated), and abcb11b mutants (panel F and Supplemental Figure 2). (A) PCA shows that transcriptomes from mtm zebrafish segregated together and were distinct when compared with WT and the other pathologic conditions. (B) Volcano plot showing differential expression between mtm and WT livers. There were 797 transcripts upregulated and 561 transcripts downregulated in the mtm mutants (absolute [log₂ fold change (FC)] >2 vs. WT, adjusted P = 0.05). (C) Venn diagrams comparing mtm fish with abcb11b-knockout fish. These transcriptomes had little overlap. (D) Venn diagrams showing comparisons between mtm zebrafish and fish treated with a high-fat diet or alcohol. In general, the individual transcriptomes were distinct and with little overlap. (E) Direct interrogation of transcripts from genes encoding canalicular transport proteins. There were no statistically significant changes between WT and mtm zebrafish, indicating that the expression changes seen in bsep (abcb11b) and mdr1 (pgp) were at the posttranscriptional level. (F) Pathway analyses of the various conditions using the fgsea (version 1.10.1 R package) analytic tool. The most striking differences were found in pathways representing inflammation and immune responses, which are shared in part between mtm and abcb11b mutants.