Role of alpha- and beta-adrenergic receptors in cardiomyocyte differentiation from murine-induced pluripotent stem cells
| Autor: | Li Xiaoli, Lu Ding, Dong-Bo Ou, Song Yan, Wen-Ju Li, Qiangsun Zheng, Bin Wang, Ting Wei, Chen Yan, Di Zeng |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epinephrine Adrenergic receptor Adrenergic beta-Antagonists Induced Pluripotent Stem Cells Apoptosis Embryoid body Biology Mice 03 medical and health sciences Troponin T Receptors Adrenergic beta Animals Myocyte Myocytes Cardiac Induced pluripotent stem cell Receptor Cells Cultured Embryoid Bodies Cell Proliferation Cell growth Cell Differentiation Original Articles Cell Cycle Checkpoints Cell Biology General Medicine Adrenergic beta-Agonists Receptors Adrenergic alpha Hedgehog signaling pathway GATA4 Transcription Factor Cell biology 030104 developmental biology Microscopy Fluorescence Immunology Homeobox Protein Nkx-2.5 Stem cell Signal Transduction |
| Zdroj: | Cell Proliferation. 50:e12310 |
| ISSN: | 0960-7722 |
| DOI: | 10.1111/cpr.12310 |
| Popis: | Objectives Induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a promising source of cells for regenerative heart disease therapies, but progress towards their use has been limited by their low differentiation efficiency and high cellular heterogeneity. Previous studies have demonstrated expression of adrenergic receptors (ARs) in stem cells after differentiation; however, roles of ARs in fate specification of stem cells, particularly in cardiomyocyte differentiation and development, have not been characterized. Materials and methods Murine-induced pluripotent stem cells (miPSCs) were cultured in hanging drops to form embryoid bodies, cells of which were then differentiated into cardiomyocytes. To determine whether ARs regulated miPSC differentiation into cardiac lineages, effects of the AR agonist, epinephrine (EPI), on miPSC differentiation and underlying signalling mechanisms, were evaluated. Results Treatment with EPI, robustly enhanced miPSC cardiac differentiation, as indicated by increased expression levels of cardiac-specific markers, GATA4, Nkx2.5 and Tnnt2. Although β-AR signalling is the foremost signalling pathway in cardiomyocytes, EPI-enhanced cardiac differentiation depended more on α-AR signalling than β-AR signalling. In addition, selective activation of α1-AR signalling with specific agonists induced vigorous cardiomyocyte differentiation, whereas selective activation of α2- or β-AR signalling induced no or less differentiation, respectively. EPI- and α1-AR-dependent cardiomyocyte differentiation from miPSCs occurred through specific promotion of CPC proliferation via the MEK-ERK1/2 pathway and regulation of miPS cell-cycle progression. Conclusions These results demonstrate that activation of ARs, particularly of α1-ARs, promoted miPSC differentiation into cardiac lineages via MEK-ERK1/2 signalling. |
| Databáze: | OpenAIRE |
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