Title Page
Contents
ABSTRACT 8
Ⅰ. Introduction 10
Ⅱ. Material and methods 14
2.1. Meta-analysis using mRNA seq data 14
2.2. Cell culture 14
2.3. Generation of hPSC-CMs and induction of maturation via Fenofibrate treatment 15
2.4. Western blot 16
2.5. Immunofluorescence staining 17
2.6. Mitochondrial bioenergetic analysis 18
2.7. Multi-electrode assay (MEA) 19
2.8. Statistical Analysis 20
Ⅲ. Results 21
3.1. Gene profiling of in vivo human fetal heart and adult heart through meta-analysis 21
3.2. Treatment with Fenofibrate, a PPARα agonist, promotes maturation of hPSC-CMs 24
3.3. Feno promotes structural maturation of hPSC-CMs 27
3.4. Feno promotes mitochondrial metabolism maturation of hPSC- CMs 30
3.5. Feno promotes electrophysiological signal maturation of hPSC- CMs 34
3.6. Verification of PPARα correlation in maturation via treatment with both Feno and GW6471, a PPARα antagonist 37
3.7. Analysis of drug reactivity between CTL and Feno through MEA 42
Ⅳ. Discussion 47
References 52
Abstract (in Korean) 57
Figure 1. Comparison of genetic profiling of fetal and adult hearts through meta-analysis. 23
Figure 2. Treatment of Fenofibrate for maturation of hPSC-CMs. 26
Figure 3. Structural maturation in hPSC-CMs following Feno treatment. 29
Figure 4. Mitochondrial based metabolism maturation in hPSC-CMs following Feno treatment. 32
Figure 5. Electrophysiological signals maturation in hPSC-CMs following Feno treatment. 36
Figure 6. Analysis of maturation of hPSC-CMs according to the counteracting effect of Feno by GW6147 treatment. 40
Figure 7. Comparison of drug response between CTL and Feno treated with proarrhythmia-induced drugs. 45