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Myofibrillar Structural Variability Underlies Contractile Function in Stem Cell-Derived Cardiomyocytes.
Ufford, Kathryn; Friedline, Sabrina; Tong, Zhaowen; Tang, Vi T; Dobbs, Amani S; Tsan, Yao-Chang; Bielas, Stephanie L; Liu, Allen P; Helms, Adam S.
Affiliation
  • Ufford K; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Friedline S; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Tong Z; Department of Biophysics, University of Michigan, Ann Arbor, MI, USA.
  • Tang VT; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Dobbs AS; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Tsan YC; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Bielas SL; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Neuroscience, University of Michigan, Ann Arbor, MI, USA.
  • Liu AP; Department of Biophysics, University of Michigan, Ann Arbor, MI, USA; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Program, University of Michigan, An
  • Helms AS; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. Electronic address: adamhelm@umich.edu.
Stem Cell Reports ; 16(3): 470-477, 2021 03 09.
Article in En | MEDLINE | ID: mdl-33577793
ABSTRACT
Disease modeling and pharmaceutical testing using cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) requires accurate assessment of contractile function. Micropatterning iPSC-CMs on elastic substrates controls cell shape and alignment to enable contractile studies, but determinants of intrinsic variability in this system have been incompletely characterized. The objective of this study was to determine the impact of myofibrillar structure on contractile function in iPSC-CMs. Automated analysis of micropatterned iPSC-CMs labeled with a cell-permeant F-actin dye revealed that myofibrillar abundance is widely variable among iPSC-CMs and strongly correlates with contractile function. This variability is not reduced by subcloning from single iPSCs and is independent of the iPSC-CM purification method. Controlling for myofibrillar structure reduces false-positive findings related to batch effect and improves sensitivity for pharmacologic testing and disease modeling. This analysis provides compelling evidence that myofibrillar structure should be assessed concurrently in studies investigating contractile function in iPSC-CMs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / Myofibrils Type of study: Prognostic_studies Limits: Humans Language: En Journal: Stem Cell Reports Year: 2021 Document type: Article Affiliation country: Estados Unidos
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / Myofibrils Type of study: Prognostic_studies Limits: Humans Language: En Journal: Stem Cell Reports Year: 2021 Document type: Article Affiliation country: Estados Unidos