Gene expression changes in human iPSC-derived cardiomyocytes after X-ray irradiation

Area of Science:

• Cardiology
• Molecular Biology
• Radiation Oncology

Background:

• Radiation-induced heart disease (RIHD) presents diverse cardiovascular effects.
• Research is limited by scarce clinical samples and suitable models.
• Previous studies observed electrophysiological changes post-irradiation.

Purpose of the Study:

• Elucidate molecular mechanisms of RIHD-related electrophysiological changes.
• Investigate gene expression alterations in cardiomyocytes after radiation exposure.
• Identify novel therapeutic targets for radiation-induced cardiac damage.

Main Methods:

• Utilized RNA deep-sequencing on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
• Irradiated hiPSC-CMs with 5 Gy X-ray and analyzed gene expression 48 hours post-exposure.
• Validated findings using quantitative real-time PCR (qRT-PCR) and compared with public myocardial data.

Main Results:

• Identified 39 upregulated and 481 downregulated genes post-irradiation.
• Observed significant alterations in genes related to cell cycle, cardiac calcium homeostasis (PDE3B), oxidative stress (FDXR, SPATA18), and cardiomyopathy (SGCD, BBC3, GDF15).

Conclusions:

• hiPSC-CMs offer a relevant model for studying responses to radiation and other stressors.
• Highlighted genes and pathways provide a foundation for functional studies in RIHD.
• Findings pave the way for developing targeted interventions against radiation-induced cardiac damage.