Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing
| Autor: | Aviv Regev, Vincent L. Butty, B. Alexander Yi, Miao-Ping Chien, Karthik Shekhar, Christopher A. Werley, Laurie A. Boyer, Jellert Gaublomme, Joel M. Kralj, William Bloxham, Adam E. Cohen |
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| Přispěvatelé: | 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, Pesce, Maurizio |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Physiology Molecular biology Cellular differentiation lcsh:Medicine Gene Expression Action Potentials Geometry Cardiovascular Sequencing techniques Gene expression Medicine and Health Sciences Myocyte Myocytes Cardiac Induced pluripotent stem cell lcsh:Science Cells Cultured Multidisciplinary Cultured Stem Cell Research - Induced Pluripotent Stem Cell - Human Cardiac electrophysiology RNA sequencing Cell Differentiation Calcium Imaging 3. Good health Cell biology Electrophysiology Heart Disease Bioassays and Physiological Analysis Biological Cultures Cardiac Sequence Analysis Transcription Research Article General Science & Technology Imaging Techniques Cells 1.1 Normal biological development and functioning Induced Pluripotent Stem Cells Neurophysiology Neuroimaging Biology Research and Analysis Methods Membrane Potential 03 medical and health sciences Calcium imaging Genetic Underpinning research Fluorescence Imaging Genetics Humans Stem Cell Research - Embryonic - Human Myocytes Stem Cell Research - Induced Pluripotent Stem Cell Sequence Analysis RNA lcsh:R Electrophysiological Techniques Biology and Life Sciences Cell Cultures Stem Cell Research Embryonic stem cell Electrophysiological Phenomena 030104 developmental biology Molecular biology techniques Biophysics RNA lcsh:Q Calcium Cardiac Electrophysiology Neuroscience |
| Zdroj: | PLoS PLoS ONE PloS one, vol 12, iss 3 PLoS ONE, Vol 12, Iss 3, p e0172671 (2017) |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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