The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus–Baf60c axis in embryonic stem cell cardiomyogenesis

D’Aniello, Cristina; Fiorenzano, Alessandro; Iaconis, Salvatore; Liguori, Giovanna L.; Andolfi, Gennaro; Cobellis, Gilda; Fico, Annalisa; Minchiotti, Gabriella

doi:10.1093/cvr/cvt166

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…A similar role for BAF60c as a key SWI/SNF target of signaling has been found in the heart, where BAF60c is essential to commit mesodermal-derived multipotent progenitors into cardiomyocytes, by mediating interactions between lineage-specific transcription factors Gata4 and Tbx5 and SWI/SNF to promote the expression of cardiogenic genes, upon nodal and BMP inhibition by endodermal-derived Cerberus 1 [22, 40]. …”

Section: Swi/snf and Embryonic Stem Cell Commitment To The Myogenic Lmentioning

confidence: 77%

SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis

Toto

Puri

Albini

2016

Cell. Mol. Life Sci.

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SWI/SNF chromatin-remodeling complexes are key regulators of the epigenetic modifications that determine whether stem cells maintain pluripotency or commit toward specific lineages through development and during postnatal life. Dynamic combinatorial assembly of multiple variants of SWI/SNF subunits is emerging as the major determinant of the functional versatility of SWI/SNF. Here, we summarize the current knowledge on the structural and functional properties of the alternative SWI/SNF complexes that direct stem cell fate toward skeletal muscle lineage and control distinct stages of skeletal myogenesis. In particular, we will refer to recent evidence pointing to the essential role of two SWI/SNF components not expressed in embryonic stem cells—the catalytic subunit BRM and the structural component BAF60C—whose induction in muscle progenitors coincides with the expansion of their transcriptional repertoire.

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Section: Swi/snf and Embryonic Stem Cell Commitment To The Myogenic Lmentioning

confidence: 77%

SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis

Toto

Puri

Albini

2016

Cell. Mol. Life Sci.

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“…Interestingly, it was reported that another member of Cerberus family, Cerl1 acts as an early but not as a later cardiac inductor in Xenopus and in chicken [26], [27]. Moreover, Cerl1 has been described to be in the same regulatory network as Baf60c in mouse embryonic stem cells (mESC) cardiogenesis [28], [29]. All this prompted us to analyze whether the absence of Cerl2 signals alters the levels of Baf60c during cardiogenesis in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…We analyzed exclusively animals that did not show LD. Besides, emerging data has elucidated the role of Cerl-1 , another member of Cer/Dan family, for cardiogenesis initiation, as reported in Xenopus [26], chicken [27] and in mouse embryonic stem cells [28], [29].…”

Section: Introductionmentioning

confidence: 94%

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

2014

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Previous analysis of the Cerberus like 2 knockout (Cerl2−/−) mouse revealed a significant mortality during the first day after birth, mostly due to cardiac defects apparently associated with randomization of the left-right axis. We have however, identified Cerl2-associated cardiac defects, particularly a large increase in the left ventricular myocardial wall in neonates that cannot be explained by laterality abnormalities. Therefore, in order to access the endogenous role of Cerl2 in cardiogenesis, we analyzed the embryonic and neonatal hearts of Cerl2 null mutants that did not display a laterality phenotype. Neonatal mutants obtained from the compound mouse line Cer2−/−::Mlc1v-nLacZ24+, in which the pulmonary ventricle is genetically marked, revealed a massive enlargement of the ventricular myocardium in animals without laterality defects. Echocardiography analysis in Cerl2−/− neonates showed a left ventricular systolic dysfunction that is incompatible with a long lifespan. We uncovered that the increased ventricular muscle observed in Cerl2−/− mice is caused by a high cardiomyocyte mitotic index in the compact myocardium which is mainly associated with increased Ccnd1 expression levels in the left ventricle at embryonic day (E) 13. Interestingly, at this stage we found augmented left ventricular expression of Cerl2 levels when compared with the right ventricle, which may elucidate the regionalized contribution of Cerl2 to the left ventricular muscle formation. Importantly, we observed an increase of phosphorylated Smad2 (pSmad2) levels in embryonic (E13) and neonatal hearts indicating a prolonged TGFβs/Nodal-signaling activation. Concomitantly, we detected an increase of Baf60c levels, but only in Cerl2−/− embryonic hearts. These results indicate that independently of its well-known role in left-right axis establishment Cerl2 plays an important role during heart development in the mouse, mediating Baf60c levels by exerting an important control of the TGFβs/Nodal-signaling pathway.

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“…This result is consistent with another report indicating the role of apelin in the cardiomyogenic differentiation of ESCs. D’Aniello et al (, ) found that apelin is involved in cardiac differentiation of ESCs via the MAPK pathway. The expression of the APJ receptor regulates the differentiation process in ESCs, and its downregulation impairs cardiac differentiation of stem cells. Apelin increases the paracrine effects of stem cells: Some scientists suggest that apelin‐treated stem/progenitor cells participate in cardiovascular regeneration through angiogenesis and their paracrine effects but not via differentiation.…”

Section: Apelin and Stem Cells: Effects On Cardiovascular Systemmentioning

confidence: 99%

Section: Apelin and Stem Cells: Effects On Cardiovascular Systemmentioning

confidence: 99%

Apelin and stem cells: the role played in the cardiovascular system and energy metabolism

Esmaeili

Bandarian

Esmaeili

et al. 2019

Cell Biology International

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Apelin, a member of the adipokine family, is widely distributed in the body and exerts cytoprotective effects on many organs. Apelin isoforms are involved in different physiological processes, including regulation of the cardiovascular system, cardiac contractility, angiogenesis, and energy metabolism. Several investigations have been performed to study the effect of apelin on stem cell therapy. This review aims to summarize the literature representing the effects of apelin on stem cell properties. Furthermore, this review discusses the therapeutic potential of apelin-treated stem cells for cardiovascular diseases and demonstrates the effect of stem cells overexpressing apelin on energy metabolism. Stem cells with their unique characteristics play a crucial role in the maintenance of tissue integrity. These cells participate in tissue regeneration via multiple mechanisms. Although preclinical and clinical studies have demonstrated the therapeutic potential of stem cells in various diseases, their application in regenerative medicine has not been efficient. A number of strategies such as genetic modification or treatment of stem cells with different factors have been used to improve the efficacy of cell therapy and to increase their survival after transplantation. This article reviews the effect of apelin treatment on the efficacy of cell therapy.

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The G-protein-coupled receptor APJ is expressed in the second heart field and regulates Cerberus–Baf60c axis in embryonic stem cell cardiomyogenesis

Abstract: We propose a model in which Apj controls a regulatory Cerberus-Baf60c pathway in pluripotent stem cell cardiomyogenesis, and speculate that this regulatory circuit may regulate cardiac progenitor cell behaviour.

Cited by 21 publications

References 37 publications

SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis

SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

Apelin and stem cells: the role played in the cardiovascular system and energy metabolism

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