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Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling

Human induced pluripotent stem cells (hiPSC) offer an unprecedented opportunity to generate model systems that facilitate a mechanistic understanding of human disease. Current differentiation protocols are capable of generating cardiac myocytes (hiPSC-CM) and sympathetic neurons (hiPSC-SN). However,...

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Autores principales: Li, Ni, Edel, Michael, Liu, Kun, Denning, Chris, Betts, Jacob, Neely, Oliver C., Li, Dan, Paterson, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150199/
https://www.ncbi.nlm.nih.gov/pubmed/37122212
http://dx.doi.org/10.1098/rstb.2022.0173
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author Li, Ni
Edel, Michael
Liu, Kun
Denning, Chris
Betts, Jacob
Neely, Oliver C.
Li, Dan
Paterson, David J.
author_facet Li, Ni
Edel, Michael
Liu, Kun
Denning, Chris
Betts, Jacob
Neely, Oliver C.
Li, Dan
Paterson, David J.
author_sort Li, Ni
collection PubMed
description Human induced pluripotent stem cells (hiPSC) offer an unprecedented opportunity to generate model systems that facilitate a mechanistic understanding of human disease. Current differentiation protocols are capable of generating cardiac myocytes (hiPSC-CM) and sympathetic neurons (hiPSC-SN). However, the ability of hiPSC-derived neurocardiac co-culture systems to replicate the human phenotype in disease modelling is still in its infancy. Here, we adapted current methods for efficient and replicable induction of hiPSC-CM and hiPSC-SN. Expression of cell-type-specific proteins were confirmed by flow cytometry and immunofluorescence staining. The utility of healthy hiPSC-CM was tested with pressor agents to develop a model of cardiac hypertrophy. Treatment with angiotensin II (AngII) resulted in: (i) cell and nuclear enlargement, (ii) enhanced fetal gene expression, and (iii) FRET-activated cAMP responses to adrenergic stimulation. AngII or KCl increased intracellular calcium transients in hiPSC-SN. Immunostaining in neurocardiac co-cultures demonstrated anatomical innervation to myocytes, where myocyte cytosolic cAMP responses were enhanced by forskolin compared with monocultures. In conclusion, human iPSC-derived cardiac myocytes and sympathetic neurons replicated many features of the anatomy and (patho)physiology of these cells, where co-culture preparations behaved in a manner that mimicked key physiological responses seen in other mammalian systems. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
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spelling pubmed-101501992023-05-02 Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling Li, Ni Edel, Michael Liu, Kun Denning, Chris Betts, Jacob Neely, Oliver C. Li, Dan Paterson, David J. Philos Trans R Soc Lond B Biol Sci Part IV: Autonomic G-Protein Mediated Modulation Human induced pluripotent stem cells (hiPSC) offer an unprecedented opportunity to generate model systems that facilitate a mechanistic understanding of human disease. Current differentiation protocols are capable of generating cardiac myocytes (hiPSC-CM) and sympathetic neurons (hiPSC-SN). However, the ability of hiPSC-derived neurocardiac co-culture systems to replicate the human phenotype in disease modelling is still in its infancy. Here, we adapted current methods for efficient and replicable induction of hiPSC-CM and hiPSC-SN. Expression of cell-type-specific proteins were confirmed by flow cytometry and immunofluorescence staining. The utility of healthy hiPSC-CM was tested with pressor agents to develop a model of cardiac hypertrophy. Treatment with angiotensin II (AngII) resulted in: (i) cell and nuclear enlargement, (ii) enhanced fetal gene expression, and (iii) FRET-activated cAMP responses to adrenergic stimulation. AngII or KCl increased intracellular calcium transients in hiPSC-SN. Immunostaining in neurocardiac co-cultures demonstrated anatomical innervation to myocytes, where myocyte cytosolic cAMP responses were enhanced by forskolin compared with monocultures. In conclusion, human iPSC-derived cardiac myocytes and sympathetic neurons replicated many features of the anatomy and (patho)physiology of these cells, where co-culture preparations behaved in a manner that mimicked key physiological responses seen in other mammalian systems. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’. The Royal Society 2023-06-19 2023-05-01 /pmc/articles/PMC10150199/ /pubmed/37122212 http://dx.doi.org/10.1098/rstb.2022.0173 Text en © 2023 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Part IV: Autonomic G-Protein Mediated Modulation
Li, Ni
Edel, Michael
Liu, Kun
Denning, Chris
Betts, Jacob
Neely, Oliver C.
Li, Dan
Paterson, David J.
Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title_full Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title_fullStr Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title_full_unstemmed Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title_short Human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
title_sort human induced pluripotent stem cell-derived cardiac myocytes and sympathetic neurons in disease modelling
topic Part IV: Autonomic G-Protein Mediated Modulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150199/
https://www.ncbi.nlm.nih.gov/pubmed/37122212
http://dx.doi.org/10.1098/rstb.2022.0173
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