|
Fig. 4 Cdk4/6 inhibition by Palbociclib (PD) rescues abnormal cell cycle gene expression in uhrf1 mutants. (A) PCA analysis of RNA Seq from 120 hpf Palbociclib (PD) treated and DMSO treated uhrf1−/− and control livers. (B) Venn diagram of differential expressed genes (DEGs) (cutoff P-adj < 0.05) between uhrf1−/− and their control siblings treated with DMSO and PD. (C) Unsupervised clustering heatmap of the expression profile of 120 hpf DMSO and PD treated uhrf1−/− liver. z-scores based on raw counts. Rows are divided into 10 clusters calculated on the hierarchical clustering of dendrogram (Euclidean distance). (D) REVIGO gene ontology of cluster 4 and (E) and cluster 5. (F) Key cell cycle genes, immune and tnfa response gene expression between PD and DMSO treated uhrf1−/− plotted as a heatmap with log2fold change. (G) IPA of the cell cycle genes differentially expressed between 120 hpf uhrf1−/− PD and DMSO livers, cell cycle checkpoint regulation pathways indicated in bold. P-value *< 0.05, **< 0.005, *** < 0.0005 by unpaired Student's t-test with adjustment for multiple comparisons and represented as median with range.