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Comparison of gene expression between human and mouse iPSC-derived cardiomyocytes for stem cell therapies of cardiovascular defects via bioinformatic analysis

Bellman, Ryan; Chen, Jishizhan; Chen, Lidan; Nomikou, Nikolitsa; Tsui, Janice; Hamilton, George; Song, Wenhui; (2023) Comparison of gene expression between human and mouse iPSC-derived cardiomyocytes for stem cell therapies of cardiovascular defects via bioinformatic analysis. Translational Medicine Communications , 8 (1) , Article 9. 10.1186/s41231-023-00139-7. Green open access

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Abstract

Background: Preclinical studies have demonstrated the potential use of induced pluripotent stem cells (iPSCs) to treat cardiovascular disease (CVD). In vivo preclinical studies conducted on animal models (murine, porcine, guinea pig, etc.) have employed either syngeneic or human-derived iPSCs. However, no study has been carried out to investigate and report the key genetic differences between the human and animal-derived iPSCs. Our study analysed the gene expression profile and molecular pathway patterns underlying the differentiation of both human and mouse iPSCs to iPSC-cardiomyocytes (iPSC-CMs), and the differences between them via bioinformatic analysis. Method: Data sets were downloaded from the Gene Expression Omnibus (GEO) database and included both human and mouse models, and the data for undifferentiated iPSCs and iPSC-CMs were isolated from each. Differentially expressed genes (DEGs) were screened and then analysed. The website g:Profiler was used to obtain the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) networks of the DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The subclusters were then extracted from the PPI network for further analysis. Results: iPSC-derived cardiomyocytes expressed many genes related to vascular, endothelial, and smooth muscle repair in the human iPSC-CMs, and prevention of calcification in the mouse iPSC-CMs with clear differences in gene expression, which will affect how iPSCs act in research. Especially in the human iPSC-CMs, and also prevention of calcification processes in the mouse data. The identified differences in gene expression of iPSCs derived from the two species suggests that in vivo studies using mouse iPSC-CMs may not reflect those in humans. Conclusion: The study provides new insights into the key genes related to the iPSCs, including genes related to angiogenesis, calcification, and striated muscle, endothelium, and bone formation. Moreover, the clear differences between both mouse and human-derived iPSCs have been identified, which could be used as new evidence and guidance for developing novel targeted therapy strategies to improve the therapeutic effects of iPSC treatment in cardiovascular defects.

Type: Article
Title: Comparison of gene expression between human and mouse iPSC-derived cardiomyocytes for stem cell therapies of cardiovascular defects via bioinformatic analysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s41231-023-00139-7
Publisher version: https://doi.org/10.1186/s41231-023-00139-7
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Bioinformatics, iPSCs, Cardiomyocytes, Enrichment analysis, Cardiovascular disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10166925
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