Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2017
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| Online Access: | http://hdl.handle.net/1721.1/109971 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0001-8567-2049 |
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| author | 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 Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 Regev, Aviv |
| author_sort | Gaublomme, Jellert |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T11:13:27Z |
| format | Article |
| id | mit-1721.1/109971 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:13:27Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1099712022-09-27T18:00:28Z Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing 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 Regev, Aviv Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Butty, Vincent L G Boyer, Laurie Ann Regev, Aviv 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 National Science Foundation (U.S.). Center on Emergent Behaviors of Integrated Cellular Systems (CBET-0939511) National Cancer Institute (U.S.) (BioMicro Center. Award P30-CA14051) Howard Hughes Medical Institute 2017-06-16T18:41:35Z 2017-06-16T18:41:35Z 2017-03 2016-09 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/109971 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. https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1371/journal.pone.0172671 PLOS ONE Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | 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 Regev, Aviv Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title | Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title_full | Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title_fullStr | Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title_full_unstemmed | Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title_short | Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing |
| title_sort | geometry dependent functional changes in ipsc derived cardiomyocytes probed by functional imaging and rna sequencing |
| url | http://hdl.handle.net/1721.1/109971 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0001-8567-2049 |
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