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

Abstract

Purpose: Radiation-induced heart disease caused by cardiac exposure to ionizing radiation comprises a variety of cardiovascular effects. Research in this field has been hampered by limited availability of clinical samples and appropriate test models. In this study, we wanted to elucidate the molecular mechanisms underlying electrophysiological changes, which we have observed in a previous study.

Materials and methods: We employed RNA deep-sequencing of human-induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) 48 h after 5 Gy X-ray irradiation. By comparison to public data from hiPSC-CMs and human myocardium, we verified the expression of cardiac-specific genes in hiPSC-CMs. Results were validated by qRT-PCR.

Results: Differentially gene expression analysis identified 39 and 481 significantly up- and down-regulated genes after irradiation, respectively. Besides, a large fraction of genes associated with cell cycle processes, we identified genes implicated in cardiac calcium homeostasis (PDE3B), oxidative stress response (FDXR and SPATA18) and the etiology of cardiomyopathy (SGCD, BBC3 and GDF15).

Conclusions: Notably, observed gene expression characteristics specific to hiPSC-CMs might be relevant regarding further investigations of the response to external stressors like radiation. The genes and biological processes highlighted in our study present promising starting points for functional follow-up studies for which hiPSC-CMs could pose an appropriate cell model when cell type specific peculiarities are taken into account.

Keywords:

• Radiation-induced heart disease
• hiPSC-CMs
• gene expression
• RNASeq

Acknowledgment

The excellent work of Richard Obermair, Gabriele Schröder, Sven Doucha-Senf, Thomas Müller, and Lisa Fees in the laboratory was highly appreciated.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Benjamin V. Becker

Benjamin V. Becker, MD, a Postdoctoral research fellow, resident in radiology.

Matthäus Majewski

Matthäus Majewski, MD, a Postdoctoral research fellow, resident in urology, Bundeswehr Institute of Radiobiology, Munich, Germany.

Michael Abend

Michael Abend, MD, M.Sc., a University Professor, Department Head Genomics I, Bundeswehr Institute of Radiobiology, Munich, Germany.

Andreas Palnek

Andreas Palnek, Laboratory assistant, an expert in cell culture, Bundeswehr Institute of Radiobiology, Munich, Germany.

Kai Nestler

Kai Nestler, MD, a Postdoctoral research fellow, resident in radiology, Bundeswehr Institute for Preventive Medicine, Koblenz, Germany.

Matthias Port

Matthias Port, MD, a University Professor, Head of the Bundeswehr Institute of Radiobiology, Specialist in Oncology and Internal Medicine.

Reinhard Ullmann

Reinhard Ullmann, Department Head Genomics II.