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Lookup NU author(s): Dr Ian CowellORCiD, John CasementORCiD, Dr Adam CreighORCiD, Dr Chunbo Yang, Professor Majlinda LakoORCiD, Professor Lyle ArmstrongORCiD, Emerita Professor Caroline AustinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026. Published by The Company of BiologistsThe role of DNA topoisomerase II beta (TOP2B) in cardiomyocyte differentiation is poorly understood. To address this, human induced pluripotent stem cells (hiPSC) were differentiated into cardiomyocytes (CM) that were wild type (WT) or contained a genomic deletion of Topoisomerase 2B (BKO). Both WT and BKO hiPSC could be induced to differentiate into sheets of beating cardiomyocytes. BKO hiPSC take slightly longer to differentiate into sheets of beating CM than WT iPSC. RNA was prepared from both undifferentiated and differentiated WT and BKO hiPSC. RNA-seq was used to examine gene expression changes when the WT and BKO hiPSC were differentiated into CM. Gene expression changes following differentiation of BKO cells were largely similar to those in WT cells. In addition, the differentiated WT CM were treated with dexrazoxane (ICRF-187), a TOP2 catalytic inhibitor that targets both TOP2A and TOP2B, or topobexin, a new TOP2B selective catalytic inhibitor. Topobexin inhibition partially phenocopied a TOP2B deletion and thereby providing an alternative to TOP2B gene knockout in many cell lines. In future, hiPSC derived CM with and without TOP2B and inhibition by topobexin ex vivo CM could be used to study anthracycline-induced cardiotoxicity and to screen for cardioprotectants.
Author(s): Kerestes V, Cowell I, Jirkovska A, Khazeem M, Karabanovich G, Melnikova I, Casement J, Kubes J, Simunek T, Roh J, Schellenberg M, Creigh A, Yang C, Lako M, Armstrong L, Austin C
Publication type: Article
Publication status: Published
Journal: Biology Open
Year: 2026
Volume: 15
Issue: 8
Online publication date: 12/08/2026
Acceptance date: 13/07/2026
Date deposited: 25/08/2026
ISSN (electronic): 2046-6390
Publisher: Company of Biologists Ltd
URL: https://doi.org/10.1242/bio.062592
DOI: 10.1242/bio.062592
Data Access Statement: RNA seq data is available through GEO (https://www.ncbi.nlm.nih.gov/gds), accession GSE262148. All relevant data and details of resources can be found within the article and its supplementary information. For resource queries please contact the corresponding author.
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