Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

Abstract

Purinergic signaling may be involved in embryonic development of the heart. In the present study, the effects of purinergic receptor stimulation on cardiomyogenesis of mouse embryonic stem (ES) cells were investigated. ADP or ATP increased the number of cardiac clusters and cardiac cells, as well as beating frequency. Cardiac-specific genes showed enhanced expression of α-MHC, MLC2v, α-actinin, connexin 45 (Cx45), and HCN4, on both gene and protein levels upon ADP/ATP treatment, indicating increased cardiomyogenesis and pacemaker cell differentiation. Real-time RT-PCR analysis of purinergic receptor expression demonstrated presence of P2X1, P2X4, P2X6, P2X7, P2Y1, P2Y2, P2Y4, and P2Y6 on differentiating ES cells. ATP and ADP as well as the P2X agonists β,γ-methylenadenosine 5′-triphosphate (β,γ-MetATP) and 8-bromoadenosine 5′-triphosphate (8- Br

Coupling switch of P2Y-IP3 receptors mediates differential Ca2+ signaling in human embryonic stem cells and derived cardiovascular progenitor cells

“…Moreover, distinct patterns of Ca 2+ responses to these nucleotides are observed between the hESCs and CVPCs. The Ca 2+ responses to ATP and UTP are more sensitive and stronger in the CVPCs than those in the hESCs, which may explain the recent finding that ATP treatment enhances cardiogenesis during mESC differentiation [23]. The differences could be interpreted by the distinct gene expression levels and selectivity of P2R subtypes in these cells (Fig.…”

“…They are also involved in the proliferation and cardiac differentiation of mouse (m) ESCs [23,24] and the growth of human adult cardiac progenitors [25]. In addition, G protein-mediated Ca 2+ signals play a role in the maintenance of undifferentiated state of hESCs [26].…”

P2X7 receptor in cardiovascular disease: The heart side

“…The treatment of mouse embryonic stem cell with ADP or ATP increases the number of cardiac clusters and cardiac cells. These cells express the P2X7 receptor along with P2Y1, P2Y2, P2Y4, P2Y6, P2X1, P2X4 and P2X6 during the time course of ADP and ATP‐induced differentiation . Physiologically, the P2X7 receptor expression on cardiomyocytes starts around embryonic day 18 .…”

“…Physiologically, the P2X7 receptor expression on cardiomyocytes starts around embryonic day 18 . P2X7 activation causes a stronger induction of the cardiac development program, showing a markedly increase in the expression of some cardiac‐specific genes, such as α‐Myosin heavy chain (α‐MHC), Myosin light chain 2 (MLC2v), α‐actinin and connexin 45 (Cx45) . The P2X7 expression has also been demonstrated on epicardium‐derived cells, a key embryonic cardiac developmental cell type.…”

“…These cells express the P2X7 receptor along with P2Y1, P2Y2, P2Y4, P2Y6, P2X1, P2X4 and P2X6 during the time course of ADP and ATP-induced differentiation. 132 Physiologically, the P2X7 receptor expression on cardiomyocytes starts around embryonic day 18. 133 This effect is abolished after treatment with the P2X7 antagonist A740003.…”