Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes

Paquin, Joanne; Danalache, Bogdan; Jankowski, Marek; McCann, Samuel M.; Gutkowska, Jolanta

doi:10.1073/pnas.152302499

Cited by 210 publications

(185 citation statements)

References 58 publications

(62 reference statements)

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“…00-8020, Zymed) were revealed by either the biotin-streptavidin method (no. Rudnicki and McBurney (20), with minor modifications (10). Briefly, 0.25 ϫ 10 6 cells were allowed to aggregate for 4 days in nonadhesive, bacteriological grade Petri dishes (6-cm diameter) containing 5 ml of complete medium supplemented with 10 Ϫ7 M OT or RA (10 Ϫ7 M and 10 Ϫ8 M) in the presence or absence of 10 Ϫ7 M OTA.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we showed that P19 embryonic carcinoma cells, a model of mouse embryonic stem cells, express OT receptors (OTRs), and OT stimulates the differentiation of these cells into beating cell colonies expressing ANP mRNA and cardiomyocyte-specific markers (10). Other substances reported to induce cardiomyogenesis in the P19 cell model are DMSO, retinoic acid (RA), 3,3Ј,5 triiodo-L-thyronine, and dynorphin (reviewed in ref.…”

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confidence: 99%

“…11). The importance of OT was demonstrated when OTA completely inhibited the formation of beating cells, not only in OT-but also in DMSO-induced culture (10). Another unique feature of OT is that, in addition to differentiation of embryonic P19 cells, this peptide can induce the cardiomyogenic differentiation of adult stem͞progenitor cells (12).…”

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confidence: 99%

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Oxytocin in cardiac ontogeny

Jankowski

Danalache²,

Wang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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100

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Previous studies demonstrated the presence of oxytocin (OT) and oxytocin receptors (OTRs) in the heart. The present work provides results supporting a potential role of OT in cardiomyogenesis. Here, we show a maximal OT and OTR protein level in the developing rat heart at day 21 of gestation and postnatal days 1-4, when cardiac myocytes are at a stage of intense hyperplasia. Between postnatal days 1 and 66, OT decreased linearly in all heart chambers (4.1-to 6.6-fold). Correspondingly, immunocytochemistry demonstrated that OTRs, which were eminent in postnatal cardiomyocytes, declined with age to low levels in adults. Interestingly, in coronary vasculature, OTRs developed in endothelial cells at postnatal days 12 and 22 and achieved a plateau in adult rats. These findings suggest that OT can be involved in developmental formation of the coronary vessels. In vivo, the OT͞OTR system in the fetal heart was sensitive to the actions of retinoic acid (RA), recognized as a major cardiac morphogen. RA treatment produced a significant increase (2-to 3-fold) both in the OT concentration and in the OT mRNA levels. Ex vivo, an OT antagonist inhibited RA-mediated cardiomyocyte differentiation of P19 embryonic stem cells. The decline of cardiac OT expression from infancy to adulthood of the rat and changes in cell types expressing OTR indicate a dynamic regulation of the OT system in the heart rather than constitutive expression. The results support the hypothesis that RA induces cardiomyogenesis by activation of the cardiac OT system. heart development ͉ oxytocin receptors ͉ retinoic acid ͉ oxytocin antagonist ͉ cardiomyocyte differentiation O xytocin (OT), recognized traditionally as a reproductive hormone with a major role in childbirth and lactation, is produced in high concentrations in the hypothalamic supraoptic nucleus and paraventricular nucleus, then transported from these source nuclei to the posterior pituitary by neurosecretion (1). Longitudinal studies of neural and hormonal circuits activated by experimental volume expansion have identified OT as a major regulator of cardiovascular functions (reviewed in refs. 2 and 3). OT, injected peripherally, causes a decrease of arterial pressure (4) while reducing both heart rate and the force of contractions in isolated atria (5). OT acts via neuroendocrine͞ endocrine͞paracrine pathways to release atrial natriuretic peptide (ANP) from the heart (6, 7). ANP is a potent diuretic, natriuretic, and vasorelaxant hormone that is also involved in cell growth regulation. In addition, we have demonstrated that in isolated, perfused hearts, an OT antagonist (OTA) blocks basal ANP release (7), suggesting the presence of local OT in the heart. Further study revealed cardiac OT synthesis (8), with OT being detected in the medium of cultured neonatal rat cardiomyocytes (9).Recently, we showed that P19 embryonic carcinoma cells, a model of mouse embryonic stem cells, express OT receptors (OTRs), and OT stimulates the differentiation of these cells into beating cell colonies expressing ...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Oxytocin in cardiac ontogeny

Jankowski

Danalache²,

Wang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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100

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“…Finally, a number of compounds were identified that promoted cardiomyogenic differentiation in embryonic carcinoma cell lines. These include Wnt-11 (Pandur et al 2002), dimethysulfoxide (Rudnicki et al 1990), and oxytocin (Paquin et al 2002). There is a high probability that these factors would have similar effects on ES cell differentiation.…”

Section: Identification Of Factors That Enhance Cardiomyogenic Differmentioning

confidence: 99%

Cardiac Repair by Embryonic Stem-Derived Cells

Rubart

Field

2006

Stem Cells

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Cell transplantation approaches offer the potential to promote regenerative growth of diseased hearts. It is well established that donor cardiomyocytes stably engraft into recipient hearts when injected directly into the myocardial wall. Moreover, the transplanted donor cardiomyocytes participate in a functional syncytium with the host myocardium. Thus, transplantation of donor cardiomyocytes resulted in at least partial restoration of lost muscle mass. It is also well established that embryonic stem (ES) cells differentiate into cells of ecto-, endo-, and mesodermal lineages when cultured under appropriate conditions in vitro. Robust cardiomyogenic differentiation was frequently observed in spontaneously differentiating ES cultures. Cellular, molecular and physiologic analyses indicated that ES-derived cells were bona fide cardiomyocytes, with in vitro characteristics typical for cells obtained from early stages of cardiac development. Thus, ES-derived cardiomyocytes constitute a viable source of donor cells for cell transplantation therapies.

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“…Various substances and stimuli have been used to enhance in vitro cardiomyogenesis from ES cells. These include erythropoietin [2], oxytocin [3], retinoic acid [4], ascorbic acid [5], fibroblast growth factor-2 (FGF-2), transforming growth factor-β (TGF-β) [6], insulin-like growth factor (IGF) [7], bone morphogenic proteins (BMPs) [8], and low concentrations of reactive oxygen species (ROS) [9 -14]. Although cardiomyogenic differentiation was substantially increased by different stimuli, a universal recipe for efficient and largeElectronic supplementary material The online version of this article (doi:10.1007/s11302-015-9468-1) contains supplementary material, which is available to authorized users.…”

Section: Introductionmentioning

confidence: 99%

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

Mazrouei

Sharifpanah

Bekhite

et al. 2015

Purinergic Signalling

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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

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Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes

Cited by 210 publications

References 58 publications

Oxytocin in cardiac ontogeny

Oxytocin in cardiac ontogeny

Cardiac Repair by Embryonic Stem-Derived Cells

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

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