Aberrant α-adrenergic hypertrophic response in Cardiomyocytes from human induced pluripotent cells

Gabor Földes, Elena Matsa, János Kriston-Vizi, Thomas Leja, Stefan Amisten, Ljudmila Kolker, Thusharika Kodagoda, Nazanin F. Dolatshad, Maxime Mioulane, Karine Vauchez, T. Arányi, Robin Ketteler, Michael D. Schneider, Chris Denning, Sian E. Harding

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Cardiomyocytes from human embryonic stem cells (hESC-CMs) and induced pluripotent stem cells (hiPSC-CMs) represent new models for drug discovery. Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the α-adrenoceptor (αAR) agonist phenylephrine (PE) compared to hESC-CMs. We investigated signaling at multiple levels to understand the underlying mechanism of this differential responsiveness. The expression of the normal α1AR gene, ADRA1A, was reversibly silenced during differentiation, accompanied by ADRA1B upregulation in either cell type. ADRA1B signaling was intact in hESC-CMs, but not in hiPSC-CMs. We observed an increased tonic activity of inhibitory kinase pathways in hiPSC-CMs, and inhibition of antihypertrophic kinases revealed hypertrophic increases. There is tonic suppression of cell growth in hiPSC-CMs, but not hESC-CMs, limiting their use in investigation of hypertrophic signaling. These data raise questions regarding the hiPSC-CM as a valid model for certain aspects of cardiac disease.

Original languageEnglish
Pages (from-to)905-914
Number of pages10
JournalStem Cell Reports
Volume3
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Induced Pluripotent Stem Cells
Cardiac Myocytes
Adrenergic Agents
Stem cells
Phosphotransferases
Cell growth
Phenylephrine
Adrenergic Receptors
Genes
Drug Discovery
Hypertrophy
Heart Diseases
Up-Regulation
Human Embryonic Stem Cells
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics
  • Medicine(all)

Cite this

Földes, G., Matsa, E., Kriston-Vizi, J., Leja, T., Amisten, S., Kolker, L., ... Harding, S. E. (2014). Aberrant α-adrenergic hypertrophic response in Cardiomyocytes from human induced pluripotent cells. Stem Cell Reports, 3(5), 905-914. https://doi.org/10.1016/j.stemcr.2014.09.002

Aberrant α-adrenergic hypertrophic response in Cardiomyocytes from human induced pluripotent cells. / Földes, Gabor; Matsa, Elena; Kriston-Vizi, János; Leja, Thomas; Amisten, Stefan; Kolker, Ljudmila; Kodagoda, Thusharika; Dolatshad, Nazanin F.; Mioulane, Maxime; Vauchez, Karine; Arányi, T.; Ketteler, Robin; Schneider, Michael D.; Denning, Chris; Harding, Sian E.

In: Stem Cell Reports, Vol. 3, No. 5, 2014, p. 905-914.

Research output: Contribution to journalArticle

Földes, G, Matsa, E, Kriston-Vizi, J, Leja, T, Amisten, S, Kolker, L, Kodagoda, T, Dolatshad, NF, Mioulane, M, Vauchez, K, Arányi, T, Ketteler, R, Schneider, MD, Denning, C & Harding, SE 2014, 'Aberrant α-adrenergic hypertrophic response in Cardiomyocytes from human induced pluripotent cells', Stem Cell Reports, vol. 3, no. 5, pp. 905-914. https://doi.org/10.1016/j.stemcr.2014.09.002
Földes, Gabor ; Matsa, Elena ; Kriston-Vizi, János ; Leja, Thomas ; Amisten, Stefan ; Kolker, Ljudmila ; Kodagoda, Thusharika ; Dolatshad, Nazanin F. ; Mioulane, Maxime ; Vauchez, Karine ; Arányi, T. ; Ketteler, Robin ; Schneider, Michael D. ; Denning, Chris ; Harding, Sian E. / Aberrant α-adrenergic hypertrophic response in Cardiomyocytes from human induced pluripotent cells. In: Stem Cell Reports. 2014 ; Vol. 3, No. 5. pp. 905-914.
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AU - Kolker, Ljudmila

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