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Successful heart development depends on the careful orchestration of a network of transcription factors and signaling pathways. In recent years, in vitro cardiac differentiation using human pluripotent stem cells (hPSCs) has been used to uncover the intricate gene-network regulation involved in the proper formation and function of the human heart. Here, we searched for uncharacterized cardiac-development genes by combining a temporal evaluation of human cardiac specification in vitro with an analysis of gene expression in fetal and adult heart tissue. We discovered that CARDEL (CARdiac DEvelopment Long non-coding RNA; LINC00890; SERTM2) expression coincides with the commitment to the cardiac lineage. CARDEL knockout hPSCs differentiated poorly into cardiac cells, and hPSC-derived cardiomyocytes showed faster beating rates after controlled overexpression of CARDEL during differentiation. Altogether, we provide physiological and molecular evidence that CARDEL expression contributes to sculpting the cardiac program during cell-fate commitment.

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Mitochondria is not only a dynamic organelle that produces ATP, but is also an important contributor to cell functions in both development and cell death processes. These paradoxical functions of mitochondria are partially regulated by the mitochondrial permeability transition pore (mPTP), a high-conductance channel that can induce loss of mitochondrial membrane potential, impairment of cellular calcium homeostasis, oxidative stress, and a decrease in ATP production upon pathological activation. Interestingly, despite their different etiologies, several neurodegenerative diseases and heart ischemic injuries share mitochondrial dysfunction as a common element. Generally, mitochondrial impairment is triggered by calcium deregulation that could lead to mPTP opening and cell death. Several studies have shown that opening of the mPTP not only induces mitochondrial damage and cell death, but is also a physiological mechanism involved in different cellular functions. The mPTP participates in regular calcium-release mechanisms that are required for proper metabolic regulation; it is hypothesized that the transient opening of this structure could be the principal mediator of cardiac and brain development. The mPTP also plays a role in protecting against different brain and cardiac disorders in the elderly population. Therefore, the aim of this work was to discuss different studies that show this controversial characteristic of the mPTP; although mPTP is normally associated with several pathological events, new critical findings suggest its importance in mitochondrial function and cell development.

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Integrins are heterodimeric receptors composed of á and â transmembrane subunits that mediate attachment of cells to the extracellular matrix and counter-ligands such as ICAM-1 on adjacent cells. â2 integrin (CD18) associates with four different á (CD11) subunits to form an integrin subfamily, which has been reported to be expressed exclusively on leukocytes. However, recent studies indicate that â2 integrin is also expressed by other types of cells. Since the gene for â2 integrin is located in the region of human chromosome 21 associated with congenital heart defects, we postulated that it may be expressed in the developing heart. Here, we show the results from several different techniques used to test this hypothesis. PCR analyses indicated that â2 integrin and the áL, áM, and áX subunits are expressed during heart development. Immunohistochemical studies in both embryonic mouse and chicken hearts, using antibodies directed against the N- or C-terminal of â2 integrin or against its á subunit partners, showed that â2 integrin, as well as the áL, áM, and áX subunits, are expressed by the endothelial and mesenchymal cells of the atrioventricular canal and in the epicardium and myocardium during cardiogenesis. In situ hybridization studies further confirmed the presence of â2 integrin in these various locations in the embryonic heart. These results indicate that the â2 integrin subfamily may have other activities in addition to leukocyte adhesion, such as modulating the migration and differentiation of cells during the morphogenesis of the cardiac valves and myocardial walls of the heart.

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Objetivo: Comparar o crescimento volumétrico total do coraçäo (C), do miocárdio ventricular (MV) e dos coxins endocárdicos (CE) entre si e com o crescimento do embriäo. Coleçäo de embriöes humanos seccionados em série e corados (27 embriöes) no período pós-somítico. Os volumes de C, MV e CE foram determinados morfometricamente e correlacionados estatisticamente ao comprimento vertex-coccyx (V-C) dos embriöes pela equaçäo alométrica Y = a x**b. O crescimento cardíaco e de seus componentes MV e CE apresentou correlaçöes estatisticamente significativas (p<0,01), mas alometricamente negativas, em relaçäo ao crescimento de V-C. Isto indica que o coraçäo apresenta, mais intensamente modificaçöes na forma que no tamanho. Entretanto, em relaçäo ao coraçäo, MV é a estrutura que apresenta maior aumento relativo no segundo mês gestacional. Comparativamente, CE decresce nesse período e termina com menos de 3% do volume final do coraçäo. Os CE näo têm a importância anteriormente atribuída no desenvolvimento das valvas e dos septos cardíacos. Pelo contrário, alteraçöes no crescimento do MV devem interferir profundamente no desenvolvimento cardíaco

Purpose: To compare the volumetric growth of the whole heart (WH), ventricular myocardium (VM), and endocardial cushions (EC) among each other and in relation to the growth of the embryo. Patients and Methods: Collection of human embryos serially sectioned and stained (27 embryos) in post-somitic period. The volumes of WH, VM and EC were morphometrically determined and statistically correlated to the embryo’s crown-rump length (C-R) by using the allometric equation Y = a xb. Results: The cardiac growth, and the growth of the VM and EC, presented significant (p < 0.01) but allometically negative correlations in relation to C-R length. It indicates that cardiac changes in shape are more pronounced than in size. However, relative to the heart itself VM is the component that presents greater volumetric increase during the second month of gestation. EC decreases and end the embryonic period proper with less of 3% of the cardiac volume. Conclusion: Our quantitative results agree with more recent morphological studies which consider EC with small significance in valves and septa development, probably functioning more as a plastic component than in genesis of cardiac structures. On the contrary some lack in growth of the VM should disturb deeply cardiac development.

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