Epicardium in Heart Development

Cao, Jingli; Duca, Sierra; Cao, Jingli

doi:10.1101/cshperspect.a037192

Cited by 34 publications

(21 citation statements)

References 142 publications

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“…TNC is expressed at important steps during coronary vasculogenesis. Progenitor cells of the coronary vessels originate from the proepicardial organ (PEO) (reviewed in [34,35]) and migrate along the surface of the primitive heart tube to form the epicardium, which undergoes EMT to give rise to the coronary vasculature and interstitial fibroblasts. TNC is expressed in cells in PEO and its expression is associated with epicardial EMT [18].…”

Section: Embryonic Heart Development and Tncmentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

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Section: Embryonic Heart Development and Tncmentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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“…During the EMT, epithelial cells downregulate their epithelial gene expression, lose their unique characteristics, and activate the mesenchymal genes to increase cell viability and motility, including aggressiveness (Li et al, 2018). Recent studies have confirmed that EMT could be affected by several signaling pathways in epicardial cells, including but not limited to transforming growth factorβ (TGF-β), retinoic acid (RA), platelet-derived growth factor (PDGF), and extra-cellular matrix (ECM) components (Cao et al, 2020). EPDCs are highly plastic and have been reported to differentiate into myocardial fibroblasts, VSMCs, and pericytes (Gittenberger-de Groot et al, 2010).…”

Section: The Origin Of Epicardial Cellsmentioning

confidence: 99%

“…The Role of TCF21 in Epicardial Cells During Heart Development Studies in different animal models have delivered several molecular signatures of proepicardial cells, including the conserved transcription factors [TCF21, Wilms tumor 1(WT1), and T-box factor 18 (Tb×18)] (Cao et al, 2020). The study of Xenopus embryos showed that proepicardial cells could migrate to the heart, retain their precursor cell characteristics and impair maturity in the absence of TCF21 (Tandon et al, 2013).…”

Section: Tcf21 and Epicardial Cellsmentioning

confidence: 99%

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Shen

Wang

et al. 2020

Front. Cell Dev. Biol.

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Transcription factor 21 (TCF21) is specific for mesoderm and is expressed in the embryos' mesenchymal derived tissues, such as the epicardium. It plays a vital role in regulating cell differentiation and cell fate specificity through epithelial-mesenchymal transformation during cardiac development. For instance, TCF21 could promote cardiac fibroblast development and inhibit vascular smooth muscle cells (VSMCs) differentiation of epicardial cells. Recent large-scale genome-wide association studies have identified a mass of loci associated with coronary heart disease (CHD). There is mounting evidence that TCF21 polymorphism might confer genetic susceptibility to CHD. However, the molecular mechanisms of TCF21 in heart development and CHD remain fundamentally problematic. In this review, we are committed to providing a detailed introduction of the biological roles of TCF21 in epicardial fate determination and the development of CHD.

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“…It is not well understood how the lineage contribution by EPDCs is regulated. Growth factors (e.g., FGF10) can promote this process by either inducing EMT or stimulating the proliferation of epicardium-derived terminal cells 6, 61, 79, 80 . It is possible that the reduction of FGF9 and IGF2 in Hdac3 eko hearts accounts for decreased derivation of epicardial lineages.…”

Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Jang

Song

et al. 2021

Preprint

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Rational: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells (EPDCs) instruct myocardial growth by secreting essential factors including fibroblast growth factor 9 (FGF9) and insulin-like growth factor 2 (IGF2). However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. Objective: To understand whether and how histone deacetylase 3 (HDAC3) in the developing epicardium regulates myocardial growth. Methods and Results: We deleted Hdac3 in the developing murine epicardium and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of EPDCs. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells (MECs) also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly down-regulated in Hdac3 KO MECs. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO MECs and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO MECs. Conclusions: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322/miR-503, providing novel insights in elucidating etiology of congenital heart defects, and conceptual strategies to promote myocardial regeneration.

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Epicardium in Heart Development

Cited by 34 publications

References 142 publications

Tenascin-C in Heart Diseases—The Role of Inflammation

Tenascin-C in Heart Diseases—The Role of Inflammation

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

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