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Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture

Standard

Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture. / Faleeva, Maria; Diakonov, Ivan; Srivastava, Prashant; Ramuz, Masoud; Calamera, Gaia; Andressen, Kjetil Wessel; Bork, Nadja; Tsansizi, Lorenza; Cosson, Marie-Victoire; Bernardo, Andreia Sofia; Nikolaev, Viacheslav; Gorelik, Julia.

In: CELLS-BASEL, Vol. 11, No. 20, 3257, 17.10.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Faleeva, M, Diakonov, I, Srivastava, P, Ramuz, M, Calamera, G, Andressen, KW, Bork, N, Tsansizi, L, Cosson, M-V, Bernardo, AS, Nikolaev, V & Gorelik, J 2022, 'Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture', CELLS-BASEL, vol. 11, no. 20, 3257. https://doi.org/10.3390/cells11203257

APA

Faleeva, M., Diakonov, I., Srivastava, P., Ramuz, M., Calamera, G., Andressen, K. W., Bork, N., Tsansizi, L., Cosson, M-V., Bernardo, A. S., Nikolaev, V., & Gorelik, J. (2022). Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture. CELLS-BASEL, 11(20), [3257]. https://doi.org/10.3390/cells11203257

Vancouver

Faleeva M, Diakonov I, Srivastava P, Ramuz M, Calamera G, Andressen KW et al. Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture. CELLS-BASEL. 2022 Oct 17;11(20). 3257. https://doi.org/10.3390/cells11203257

Bibtex

@article{9fe91acd5a304dd88b811a16a0ae4a76,
title = "Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture",
abstract = "The therapeutic benefit of stimulating the cGMP pathway as a form of treatment to combat heart failure, as well as other fibrotic pathologies, has become well established. However, the development and signal compartmentation of this crucial pathway has so far been overlooked. We studied how the three main cGMP pathways, namely, nitric oxide (NO)-cGMP, natriuretic peptide (NP)-cGMP, and β3-adrenoreceptor (AR)-cGMP, mature over time in culture during cardiomyocyte differentiation from human pluripotent stem cells (hPSC-CMs). After introducing a cGMP sensor for F{\"o}rster Resonance Energy Transfer (FRET) microscopy, we used selective phosphodiesterase (PDE) inhibition to reveal cGMP signal compartmentation in hPSC-CMs at various times of culture. Methyl-β-cyclodextrin was employed to remove cholesterol and thus to destroy caveolae in these cells, where physical cGMP signaling compartmentalization is known to occur in adult cardiomyocytes. We identified PDE3 as regulator of both the NO-cGMP and NP-cGMP pathway in the early stages of culture. At the late stage, the role of the NO-cGMP pathway diminished, and it was predominantly regulated by PDE1, PDE2, and PDE5. The NP-cGMP pathway shows unrestricted locally and unregulated cGMP signaling. Lastly, we observed that maturation of the β3-AR-cGMP pathway in prolonged cultures of hPSC-CMs depends on the accumulation of caveolae. Overall, this study highlighted the importance of structural development for the necessary compartmentation of the cGMP pathway in maturing hPSC-CMs.",
keywords = "Adult, Humans, Myocytes, Cardiac/metabolism, Induced Pluripotent Stem Cells/metabolism, Nitric Oxide/metabolism, Cyclic GMP/metabolism, Phosphoric Diester Hydrolases/metabolism",
author = "Maria Faleeva and Ivan Diakonov and Prashant Srivastava and Masoud Ramuz and Gaia Calamera and Andressen, {Kjetil Wessel} and Nadja Bork and Lorenza Tsansizi and Marie-Victoire Cosson and Bernardo, {Andreia Sofia} and Viacheslav Nikolaev and Julia Gorelik",
year = "2022",
month = oct,
day = "17",
doi = "10.3390/cells11203257",
language = "English",
volume = "11",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "20",

}

RIS

TY - JOUR

T1 - Compartmentation of cGMP Signaling in Induced Pluripotent Stem Cell Derived Cardiomyocytes during Prolonged Culture

AU - Faleeva, Maria

AU - Diakonov, Ivan

AU - Srivastava, Prashant

AU - Ramuz, Masoud

AU - Calamera, Gaia

AU - Andressen, Kjetil Wessel

AU - Bork, Nadja

AU - Tsansizi, Lorenza

AU - Cosson, Marie-Victoire

AU - Bernardo, Andreia Sofia

AU - Nikolaev, Viacheslav

AU - Gorelik, Julia

PY - 2022/10/17

Y1 - 2022/10/17

N2 - The therapeutic benefit of stimulating the cGMP pathway as a form of treatment to combat heart failure, as well as other fibrotic pathologies, has become well established. However, the development and signal compartmentation of this crucial pathway has so far been overlooked. We studied how the three main cGMP pathways, namely, nitric oxide (NO)-cGMP, natriuretic peptide (NP)-cGMP, and β3-adrenoreceptor (AR)-cGMP, mature over time in culture during cardiomyocyte differentiation from human pluripotent stem cells (hPSC-CMs). After introducing a cGMP sensor for Förster Resonance Energy Transfer (FRET) microscopy, we used selective phosphodiesterase (PDE) inhibition to reveal cGMP signal compartmentation in hPSC-CMs at various times of culture. Methyl-β-cyclodextrin was employed to remove cholesterol and thus to destroy caveolae in these cells, where physical cGMP signaling compartmentalization is known to occur in adult cardiomyocytes. We identified PDE3 as regulator of both the NO-cGMP and NP-cGMP pathway in the early stages of culture. At the late stage, the role of the NO-cGMP pathway diminished, and it was predominantly regulated by PDE1, PDE2, and PDE5. The NP-cGMP pathway shows unrestricted locally and unregulated cGMP signaling. Lastly, we observed that maturation of the β3-AR-cGMP pathway in prolonged cultures of hPSC-CMs depends on the accumulation of caveolae. Overall, this study highlighted the importance of structural development for the necessary compartmentation of the cGMP pathway in maturing hPSC-CMs.

AB - The therapeutic benefit of stimulating the cGMP pathway as a form of treatment to combat heart failure, as well as other fibrotic pathologies, has become well established. However, the development and signal compartmentation of this crucial pathway has so far been overlooked. We studied how the three main cGMP pathways, namely, nitric oxide (NO)-cGMP, natriuretic peptide (NP)-cGMP, and β3-adrenoreceptor (AR)-cGMP, mature over time in culture during cardiomyocyte differentiation from human pluripotent stem cells (hPSC-CMs). After introducing a cGMP sensor for Förster Resonance Energy Transfer (FRET) microscopy, we used selective phosphodiesterase (PDE) inhibition to reveal cGMP signal compartmentation in hPSC-CMs at various times of culture. Methyl-β-cyclodextrin was employed to remove cholesterol and thus to destroy caveolae in these cells, where physical cGMP signaling compartmentalization is known to occur in adult cardiomyocytes. We identified PDE3 as regulator of both the NO-cGMP and NP-cGMP pathway in the early stages of culture. At the late stage, the role of the NO-cGMP pathway diminished, and it was predominantly regulated by PDE1, PDE2, and PDE5. The NP-cGMP pathway shows unrestricted locally and unregulated cGMP signaling. Lastly, we observed that maturation of the β3-AR-cGMP pathway in prolonged cultures of hPSC-CMs depends on the accumulation of caveolae. Overall, this study highlighted the importance of structural development for the necessary compartmentation of the cGMP pathway in maturing hPSC-CMs.

KW - Adult

KW - Humans

KW - Myocytes, Cardiac/metabolism

KW - Induced Pluripotent Stem Cells/metabolism

KW - Nitric Oxide/metabolism

KW - Cyclic GMP/metabolism

KW - Phosphoric Diester Hydrolases/metabolism

U2 - 10.3390/cells11203257

DO - 10.3390/cells11203257

M3 - SCORING: Journal article

C2 - 36291124

VL - 11

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 20

M1 - 3257

ER -