Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression
Fig 2
Differential mean 24-hour expression.
To determine whether IH impacted mean 24-hour expression, we ran a DESeq2 analysis using the Kallisto R package. (A) The transcriptome changes within liver, lung, kidney, muscle, heart, and cerebellum were examined. Based on q ≤ 0.05 and a 1.5-fold difference, significant differences with up- (orange) or down (blue)-regulated genes have been screened and presented. (B) GSEA of consistently and significantly (q ≤ 0.05) associated regulatory targets with differential gene expression in at least 4 distinct tissues. The results indicated that in the lung, muscle, and heart, MIRs were primarily associated with up-regulated genes, while the same MIRs were associated with down-regulated genes in the kidney and cerebellum. (C) GSEA of hallmark pathways for differentially expressed genes upon IH exposure. Dot size indicates absolute NES. Statistical significance was determined by (q ≤ 0.05, GSEA). Hallmark pathways in the lung and heart are highly impacted compared to those in other organs. Some of these changes in hallmark pathways overlapped with processes in other organs. Significant (p ≤ 0.05, two-way ANOVA) changes in gene expression of PHDs and/or HIFs in (D) the lung and (E) the heart after exposure to normoxia and IH. Data output for Fig 2A can be found in S1 Data, for Fig 2B in S2 Data, for Fig 2C in S3 Data. Raw and processed data files for all figures in Fig 2 accessible through GEO series accession number GSE214530. GSEA, gene set enrichment analysis; HIF, hypoxia-inducible factor; IH, intermittent hypoxia; MIR, microRNA; NES, normalized enrichment score; PHD, prolyl hydroxylase.