Display options
Cite
Gilbert G, Kadur Nagaraju C, Duelen R, et al. Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Front Cell Dev Biol. 2021;9:737840doi: 10.3389/fcell.2021.737840.
Gilbert, G., Kadur Nagaraju, C., Duelen, R., Amoni, M., Bobin, P., Eschenhagen, T., Roderick, H. L., Sampaolesi, M., & Sipido, K. R. (2021). Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Frontiers in cell and developmental biology, 9737840. https://doi.org/10.3389/fcell.2021.737840
Gilbert, Guillaume, et al. "Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes." Frontiers in cell and developmental biology vol. 9 (2021): 737840. doi: https://doi.org/10.3389/fcell.2021.737840
Gilbert G, Kadur Nagaraju C, Duelen R, Amoni M, Bobin P, Eschenhagen T, Roderick HL, Sampaolesi M, Sipido KR. Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Front Cell Dev Biol. 2021 Nov 04;9:737840. doi: 10.3389/fcell.2021.737840. eCollection 2021. PMID: 34805146; PMCID: PMC8599983.
Copy Download .nbib Format: NLM
Share it on

Front Cell Dev Biol. 2021 Nov 04;9:737840. doi: 10.3389/fcell.2021.737840. eCollection 2021.

Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Frontiers in cell and developmental biology

Guillaume Gilbert, Chandan Kadur Nagaraju, Robin Duelen, Matthew Amoni, Pierre Bobin, Thomas Eschenhagen, H Llewelyn Roderick, Maurilio Sampaolesi, Karin R Sipido

Affiliations

  1. Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
  2. Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium.
  3. Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  4. German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.

PMID: 34805146 PMCID: PMC8599983 DOI: 10.3389/fcell.2021.737840

Abstract

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex. We examined the expression of DAPC components in hiPSC-CM, which underwent maturation in 2D and 3D culture protocols. The results were compared with human adult cardiac tissue and isolated cardiomyocytes. We found that similarly to adult cardiomyocytes, hiPSC-CM express dystrophin, in line with previous studies on Duchenne's disease. β-dystroglycan was also expressed, but, contrary to findings in adult cardiomyocytes, none of the sarcoglycans nor α-dystroglycan were, despite the presence of their mRNA. In conclusion, despite the robust expression of dystrophin, the absence of several other DAPC protein components cautions for reliance on commonly used protocols for hiPSC-CM maturation for functional assessment of the complete DAPC.

Copyright © 2021 Gilbert, Kadur Nagaraju, Duelen, Amoni, Bobin, Eschenhagen, Roderick, Sampaolesi and Sipido.

Keywords: Duchenne muscular dystrophy; cardiomyopathy; dystrophin-associated glycoprotein complex; hiPSC cardiomyocyte maturation; hiPSC-derived cardiomyocytes; human induced pluripotent stem cells; sarcoglycanopathy

Conflict of interest statement

TE is co-founder of EHT Technologies GmbH, Hamburg. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as

References

  1. Circ Res. 2020 Apr 10;126(8):1086-1106 - PubMed
  2. Nat Protoc. 2017 Jun;12(6):1177-1197 - PubMed
  3. Circulation. 2017 May 9;135(19):1832-1847 - PubMed
  4. Methods Mol Biol. 2014;1181:121-9 - PubMed
  5. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(8):798-821 - PubMed
  6. Methods Mol Biol. 2012;869:205-13 - PubMed
  7. Circ Res. 2004 Apr 30;94(8):1023-31 - PubMed
  8. Front Cell Dev Biol. 2020 Mar 19;8:178 - PubMed
  9. Brain Res Dev Brain Res. 1996 Jan 22;91(1):70-82 - PubMed
  10. Am J Physiol Cell Physiol. 2010 Sep;299(3):C706-13 - PubMed
  11. Nat Commun. 2020 Jan 7;11(1):75 - PubMed
  12. Nat Rev Cardiol. 2020 Jun;17(6):341-359 - PubMed
  13. Lancet. 2019 Nov 30;394(10213):2025-2038 - PubMed
  14. Cardiovasc Res. 2020 Feb 1;116(2):368-382 - PubMed
  15. J Mol Cell Cardiol. 2020 Jan;138:1-11 - PubMed
  16. Cell Stem Cell. 2020 Jun 4;26(6):862-879.e11 - PubMed
  17. Nat Med. 2020 Feb;26(2):207-214 - PubMed
  18. Circ Res. 2017 Dec 8;121(12):1323-1330 - PubMed
  19. Sci Adv. 2018 Jan 31;4(1):eaap9004 - PubMed
  20. Genomics. 1998 Mar 1;48(2):145-56 - PubMed
  21. Circ Res. 2015 Dec 4;117(12):995-1000 - PubMed
  22. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1362-70 - PubMed
  23. J Am Coll Cardiol. 2020 Mar 17;75(10):1159-1174 - PubMed
  24. Biomaterials. 2016 Dec;111:66-79 - PubMed
  25. Stem Cell Reports. 2018 Mar 13;10(3):822-833 - PubMed
  26. J Clin Med. 2020 Feb 14;9(2): - PubMed
  27. J Cell Mol Med. 2021 Apr;25(8):3922-3934 - PubMed
  28. J Mol Cell Cardiol. 2018 May;118:147-158 - PubMed
  29. Curr Opin Cardiol. 2001 May;16(3):211-7 - PubMed
  30. Muscle Nerve. 2000 Oct;23(10):1456-71 - PubMed

Publication Types