Cargando…
Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes
The inaccessibility of human cardiomyocytes significantly hindered years of cardiovascular research efforts. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates to model th...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382583/ https://www.ncbi.nlm.nih.gov/pubmed/37507481 http://dx.doi.org/10.1038/s41598-023-39525-4 |
_version_ | 1785080703909625856 |
---|---|
author | Bourque, Kyla Jones-Tabah, Jace Pétrin, Darlaine Martin, Ryan D. Tanny, Jason C. Hébert, Terence E. |
author_facet | Bourque, Kyla Jones-Tabah, Jace Pétrin, Darlaine Martin, Ryan D. Tanny, Jason C. Hébert, Terence E. |
author_sort | Bourque, Kyla |
collection | PubMed |
description | The inaccessibility of human cardiomyocytes significantly hindered years of cardiovascular research efforts. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates to model the human heart either in vivo or through in vitro cultures. More recently, due to concerns regarding animal to human translation, including cross-species differences, the use of human iPSC-derived cardiomyocytes presented a renewed opportunity. Here, we conducted a comparative study, assessing cellular signaling through cardiac G protein-coupled receptors (GPCRs) in rat neonatal cardiomyocytes (RNCMs) and human induced pluripotent stem cell-derived cardiomyocytes. Genetically encoded biosensors were used to explore GPCR-mediated nuclear protein kinase A (PKA) and extracellular signal-regulated kinase 1/ 2 (ERK1/2) activities in both cardiomyocyte populations. To increase data granularity, a single-cell analytical approach was conducted. Using automated high content microscopy, our analyses of nuclear PKA and ERK(1/2) signaling revealed distinct response clusters in rat and human cardiomyocytes. In line with this, bulk RNA-seq revealed key differences in the expression patterns of GPCRs, G proteins and downstream effector expression levels. Our study demonstrates that human stem cell-derived models of the cardiomyocyte offer distinct advantages for understanding cellular signaling in the heart. |
format | Online Article Text |
id | pubmed-10382583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103825832023-07-30 Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes Bourque, Kyla Jones-Tabah, Jace Pétrin, Darlaine Martin, Ryan D. Tanny, Jason C. Hébert, Terence E. Sci Rep Article The inaccessibility of human cardiomyocytes significantly hindered years of cardiovascular research efforts. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates to model the human heart either in vivo or through in vitro cultures. More recently, due to concerns regarding animal to human translation, including cross-species differences, the use of human iPSC-derived cardiomyocytes presented a renewed opportunity. Here, we conducted a comparative study, assessing cellular signaling through cardiac G protein-coupled receptors (GPCRs) in rat neonatal cardiomyocytes (RNCMs) and human induced pluripotent stem cell-derived cardiomyocytes. Genetically encoded biosensors were used to explore GPCR-mediated nuclear protein kinase A (PKA) and extracellular signal-regulated kinase 1/ 2 (ERK1/2) activities in both cardiomyocyte populations. To increase data granularity, a single-cell analytical approach was conducted. Using automated high content microscopy, our analyses of nuclear PKA and ERK(1/2) signaling revealed distinct response clusters in rat and human cardiomyocytes. In line with this, bulk RNA-seq revealed key differences in the expression patterns of GPCRs, G proteins and downstream effector expression levels. Our study demonstrates that human stem cell-derived models of the cardiomyocyte offer distinct advantages for understanding cellular signaling in the heart. Nature Publishing Group UK 2023-07-28 /pmc/articles/PMC10382583/ /pubmed/37507481 http://dx.doi.org/10.1038/s41598-023-39525-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bourque, Kyla Jones-Tabah, Jace Pétrin, Darlaine Martin, Ryan D. Tanny, Jason C. Hébert, Terence E. Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title | Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title_full | Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title_fullStr | Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title_full_unstemmed | Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title_short | Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes |
title_sort | comparing the signaling and transcriptome profiling landscapes of human ipsc-derived and primary rat neonatal cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382583/ https://www.ncbi.nlm.nih.gov/pubmed/37507481 http://dx.doi.org/10.1038/s41598-023-39525-4 |
work_keys_str_mv | AT bourquekyla comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes AT jonestabahjace comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes AT petrindarlaine comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes AT martinryand comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes AT tannyjasonc comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes AT hebertterencee comparingthesignalingandtranscriptomeprofilinglandscapesofhumanipscderivedandprimaryratneonatalcardiomyocytes |