Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing
Name
Werley-2017-Geometry-dependent functional chan.pdf
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2.22 MB
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Author(s)
Gaublomme, Jellert
Shekhar, Karthik
Yi, B. Alexander
Kralj, Joel M.
Bloxham, William
Cohen, Adam E.
Werley, Christopher A.
Chien, Miao-Ping
Butty, Vincent L G
Boyer, Laurie Ann
Date Issued
March 2017
Journal
PLOS ONE
Publisher
Public Library of Science
Citation
Werley, Christopher A. et al. “Geometry-Dependent Functional Changes in iPSC-Derived Cardiomyocytes Probed by Functional Imaging and RNA Sequencing.” Ed. Maurizio Pesce. PLOS ONE 12.3 (2017): e0172671.
Version
Final published version
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned
islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes. hiPSC-CM in larger islands showed electrical and calcium dynamics indicative of greater functional maturity. We then compared transcriptional signatures of the small and large islands against a developmental time course of cardiac differentiation. Although island size had little effect on expression of most genes whose levels differed between hiPSC-CM and adult primary CM, we identified a subset of genes for which island size drove the majority (58%) of the changes associated with functional maturation. Finally, we patterned hiPSC-CM on islands with a variety of shapes to probe the relative contributions of soluble factors, electrical coupling, and direct cell-cell contacts to the functional maturation. Collectively, our data show that optical electrophysiology is a powerful tool for assaying hiPSC-CM maturation, and that island size powerfully drives activation of a subset of genes involved in cardiac maturation
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0172671
