scholarly journals Building and Repairing the Heart: What Can We Learn from Embryonic Development?

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ana G. Freire ◽  
Tatiana P. Resende ◽  
Perpétua Pinto-do-Ó
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Embryonic Stem ◽  
Cardiac Pathophysiology ◽  
Distinct Cell ◽  
Cell Sources ◽  
Cardiac Lineage ◽  
Heart Formation ◽  
Tissue Recovery

Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs)in vitromodel system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed.

GATA factors in vertebrate heart development and disease

2006 ◽  
Vol 8 (22) ◽  
pp. 1-20 ◽  
Author(s):  
Alison Brewer ◽  
John Pizzey
Keyword(s):  
Transcription Factors ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Cellular Mechanisms ◽  
Cardiac Morphogenesis ◽  
Functional Roles ◽  
Gata Factors ◽  
Evolutionarily Conserved ◽  
Heart Formation

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.

scholarly journals In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 557 ◽  
Author(s):  
Dinesh Bharti ◽  
Si-Jung Jang ◽  
Sang-Yun Lee ◽  
Sung-Lim Lee ◽  
Gyu-Jin Rho
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
In Vivo Studies ◽  
Special Focus ◽  
Morphological Alterations ◽  
Cell Sources ◽  
Induced Pluripotent

In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.

scholarly journals The Expanding Role for Retinoid Signaling in Heart Development

2008 ◽  
Vol 8 ◽  
pp. 194-211 ◽  
Author(s):  
Loretta L. Hoover ◽  
Elizabeth G. Burton ◽  
Bonnie A. Brooks ◽  
Steven W. Kubalak
Keyword(s):  
Vitamin A ◽  
Heart Development ◽  
Cardiac Development ◽  
Tube Formation ◽  
Conditional Knockout ◽  
Heart Tube ◽  
Developmental Defects ◽  
Retinoid Signaling ◽  
Developing Heart ◽  
Cardiac Lineage

The importance of retinoid signaling during cardiac development has long been appreciated, but recently has become a rapidly expanding field of research. Experiments performed over 50 years ago showed that too much or too little maternal intake of vitamin A proved detrimental for embryos, resulting in a cadre of predictable cardiac developmental defects. Germline and conditional knockout mice have revealed which molecular players in the vitamin A signaling cascade are potentially responsible for regulating specific developmental events, and many of these molecules have been temporally and spatially characterized. It is evident that intact and controlled retinoid signaling is necessary for each stage of cardiac development to proceed normally, including cardiac lineage determination, heart tube formation, looping, epicardium formation, ventricular maturation, chamber and outflow tract septation, and coronary arteriogenesis. This review summarizes many of the significant milestones in this field and particular attention is given to recently uncovered cross-talk between retinoid signaling and other developmentally significant pathways. It is our hope that this review of the role of retinoid signaling during formation, remodeling, and maturation of the developing heart will serve as a tool for future discoveries.

Vinculin knockout results in heart and brain defects during embryonic development

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 327-337 ◽  
Author(s):  
W. Xu ◽  
H. Baribault ◽  
E.D. Adamson
Keyword(s):  
Embryonic Development ◽  
Focal Adhesion ◽  
Heart Development ◽  
Cardiac Development ◽  
Es Cells ◽  
Embryonic Stem ◽  
Spinal Nerve ◽  
Cell Behaviors ◽  
Migration Rates ◽  
Targeting Vector

The vinculin gene codes for a cytoskeletal protein, found in focal adhesion plaques and in cell-cell adherens junctions. Vinculin was inactivated by homologous recombination using a targeting vector in embryonic stem (ES) cells. The heterozygous ES cells were introduced into mice by established procedures to produce heterozygous animals that were normal and fertile. No homozygous vinculin−/− embryos were born and analyses during the gestational period showed that the vinculin null embryos were small and abnormal from day E8 but some survived until E10. The most prominent defect was lack of midline fusion of the rostral neural tube, producing a cranial bilobular appearance and attenuation of cranial and spinal nerve development. Heart development was curtailed at E9.5, with severely reduced and akinetic myocardial and endocardial structures. Mutant embryos were 30–40% smaller, somites and limbs were retarded and ectodermal tissues were sparse and fragile. Fibroblasts (MEF) isolated from mutant embryos were shown to have reduced adhesion to fibronectin, vitronectin, laminin and collagen compared to wild-type levels. In addition, migration rates over these substrata were two-fold higher and the level of focal adhesion kinase (FAK) activity was three-fold higher. We conclude that vinculin is necessary for normal embryonic development, probably because of its role in the regulation of cell adhesion and locomotion, cell behaviors essential for normal embryonic morphogenesis, although specific roles in neural and cardiac development cannot be ruled out.

Abstract 78: Pnmt+ "Primer" Cells Give Rise to Cardiac Myocytes and Neurons in the Mammalian Heart: Development of New Experimental Tools for Cardiac Regenerative Medicine Applications

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Namita M Varudkar ◽  
Jixiang Xia ◽  
Ibrahim Abukenda ◽  
Karl Pfeifer ◽  
Steven Ebert
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Neural Crest ◽  
Heart Development ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Stem Cell Differentiation ◽  
Left Ventricular

Phenylethanolamine n-methyltransferase (Pnmt) catalyzes the conversion of norepinephrine to epinephrine, and thus serves as a marker for adrenergic cells. We employed a combination of immunofluorescent histochemical staining and genetic fate-mapping strategies to show that two separate Pnmt+ cell populations contribute to heart development. Intrinsic cardiac adrenergic (ICA) cells originate from the primary heart field, and contribute to pacemaking, conduction, and working (contractile) myocardium. A second population of cardiac Pnmt+ cells is derived from migrating neural crest. These neural crest adrenergic (NCA) cells appear to contribute to cardiac neurons. By adulthood, most of the Pnmt+ cells show a distinctively left-sided orientation in the heart, with nearly 90% of them being found in the left atrium and ventricle. Surprisingly large swaths of ventricular muscle are derived from Pnmt+ primer cells. Since this region of the heart is highly vulnerable to coronary artery disease and often sustains varying degrees of damage following myocardial infarction, we hypothesize that directed stem cell differentiation into Pnmt+ primer cells could serve as a valuable resource for repair and/or regeneration of left ventricular myocardium for heart disease patients. To test this hypothesis, we have generated stable recombinant mouse embryonic stem cell (mESC) lines that express various fluorescent marker proteins under the control of the endogenous Pnmt gene regulatory network. These cells can be rapidly expanded in culture, sorted, and used for transplantation studies in animal models to determine their therapeutic effectiveness. The cells can be induced along cardiogenic or neurogenic pathways in vitro, and the resulting Pnmt+ cells from each population can then be collected and tested in vivo. To achieve this goal, we have knocked-in a nuclear-localized enhanced green fluorescent protein into the Pnmt locus to create Pnmt-nEGFP recombinant mESCs and mice. We show that nEGFP expression is specifically expressed in Pnmt+ cells in vitro and in vivo. This strategy allows us to identify and isolate Pnmt+ cells to evaluate their effectiveness for cardiac regenerative medicine applications. .

Abstract 1461: Wnt2 Plays a Key Role in Cardiac Development Via a Non-Canonical Pathway

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takeshi Onizuka ◽  
Shinsuke Yuasa ◽  
Kenichiro Shimoji ◽  
Keiichi Fukuda ◽  
Satoshi Ogawa
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Early Stage ◽  
Es Cells ◽  
Embryonic Stem ◽  
Canonical Pathway ◽  
Embryonic Cells ◽  
Potent Effect ◽  
Canonical Wnt ◽  
Promising Source

Embryonic stem (ES) cells are a promising source of cardiomyocytes, but their clinical application has been hindered by the lack of selective differentiation methods. Although several signals are involved in heart development, the precise signals that mediate cardiomyocyte differentiation remain undetermined. Wnt family has a potent effect on the various organ development. To address this issue, we investigated the expression of wnt genes in the embryonic heart. Then we applied these findings to establish an efficient protocol to induce cardiomyocytes in vitro . (1) We analyzed TOP-EGFP mice to clarify whether canonical wnt signal pathway is important in the developing heart. TOP-EGFP mice are transgenic mice in which the EGFP gene is located under the β-catenin binding site so that the EGFP protein expresses when the canonical pathway is activated. They did not reveal any GFP in early stage heart, indicating that the canonical pathway is not involved. (2) Expression of non-canonical wnt was screened. Whole mount in situ hybridization of wnt2 and nkx2.5 (positive control) was performed at mouse embryo. Wnt2 was strongly expressed in the the heart-forming area in stages from E7.5 to E9.0. (3) We applied this embryonic wnt2 expression pattern to ES cell differentiation. Using siRNA we knocked-down wnt2 protein in various phases, which inhibited formation of beating EB, and decreased cardiac muscle genes only during the primitive stage (day 2– 4). Also adding wnt2 protein to embryonic cells in the appropriate phase led to a marked induction of cardiac specific genes. But wnt2 did not affect the mesodermal gene expression, Brachyury T and Mesp1, suggesting that Wnt2 does not affect the primitive development of the mesodermal progenitor cells. However, Wnt2 critically promotes cardiac specification after mesodermal induction and increases the eventual cardiac musculature. Wnt2 was strongly expressed in the heart-forming region. We applied this finding to develop an effective protocol for obtaining cardiomyocytes from mouse ES cells by adding wnt2 protein and also to inhibit generation of cardiomyocytes by inhibition of wnt2 signaling. We concluded that wnt2 plays a key role in cardiac development via a non-canonical pathway.

scholarly journals Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guizhen Du ◽  
Mingming Yu ◽  
Lingling Wang ◽  
Weiyue Hu ◽  
Ling Song ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Heart Development ◽  
Antibacterial Agent ◽  
Human Embryonic Stem Cell ◽  
Cardiac Development ◽  
Embryonic Stem ◽  
Environmental Chemicals ◽  
Cardiomyocyte Differentiation ◽  
Gene Expressions ◽  
Gata Motif

Cardiac development is a dynamic process and sensitive to environmental chemicals. Triclosan is widely used as an antibacterial agent and reported to transport across the placenta and affect embryonic development. Here, we used human embryonic stem cell- (hESC-) derived cardiomyocytes (CMs) to determine the effects of TCS exposure on cardiac development. After TCS treatment, the differentiation process was significantly blocked and spontaneous beating rates of CMs were also decreased. Transcriptome analysis showed the dysregulation of genes involved in cardiogenesis, including GATA4 and TNNT2. Additionally, DNA methylation was also altered by TCS exposure, especially in those regions with GATA motif enrichment. These alterations of transcriptome and DNA methylation were all associated with signaling pathways integral to heart development. Our findings indicate that TCS exposure might cause cardiomyocyte differentiation toxicity and provide the new insights into how environmental factors regulate DNA methylation and gene expressions during heart development.

scholarly journals Phosphodiesterases Expression during Murine Cardiac Development

2021 ◽  
Vol 22 (5) ◽  
pp. 2593
Author(s):  
Thays Maria da Conceição Silva Carvalho ◽  
Silvia Cardarelli ◽  
Mauro Giorgi ◽  
Andrea Lenzi ◽  
Andrea M. Isidori ◽  
...  
Keyword(s):  
Heart Development ◽  
Fetal Heart ◽  
Cardiac Development ◽  
Large Family ◽  
Hydrolytic Activity ◽  
Development Data ◽  
Heart Formation ◽  
Camp And Cgmp ◽  
Developing Mice

3′-5′ cyclic nucleotide phosphodiesterases (PDEs) are a large family of enzymes playing a fundamental role in the control of intracellular levels of cAMP and cGMP. Emerging evidence suggested an important role of phosphodiesterases in heart formation, but little is known about the expression of phosphodiesterases during cardiac development. In the present study, the pattern of expression and enzymatic activity of phosphodiesterases was investigated at different stages of heart formation. C57BL/6 mice were mated and embryos were collected from 14.5 to 18.5 days of development. Data obtained by qRT-PCR and Western blot analysis showed that seven different isoforms are expressed during heart development, and PDE1C, PDE2A, PDE4D, PDE5A and PDE8A are modulated from E14.5 to E18.5. In heart homogenates, the total cAMP and cGMP hydrolytic activity is constant at the evaluated times, and PDE4 accounts for the majority of the cAMP hydrolyzing ability and PDE2A accounts for cGMP hydrolysis. This study showed that a subset of PDEs is expressed in developing mice heart and some of them are modulated to maintain constant nucleotide phosphodiesterase activity in embryonic and fetal heart.

scholarly journals Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development

2006 ◽  
Vol 11 (4) ◽  
pp. 535-546 ◽  
Author(s):  
Dana Zeineddine ◽  
Evangelia Papadimou ◽  
Karim Chebli ◽  
Mathieu Gineste ◽  
Jun Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Heart Development ◽  
Embryonic Stem ◽  
Cardiac Lineage

scholarly journals Dissecting the Complexity of Early Heart Progenitor Cells

2021 ◽  
Vol 9 (1) ◽  
pp. 5
Author(s):  
Miquel Sendra ◽  
Jorge Domínguez ◽  
Miguel Torres ◽  
Oscar Ocaña
Keyword(s):  
Progenitor Cells ◽  
Heart Development ◽  
Functional Role ◽  
Cardiac Development ◽  
Heart Defects ◽  
Heart Tube ◽  
Cell Sources ◽  
Key Aspects ◽  
Functional Analyses ◽  
Lineage Diversification

Early heart development depends on the coordinated participation of heterogeneous cellsources. As pioneer work from Adriana C. Gittenberger-de Groot demonstrated, characterizing thesedistinct cell sources helps us to understand congenital heart defects. Despite decades of researchon the segregation of lineages that form the primitive heart tube, we are far from understanding itsfull complexity. Currently, single-cell approaches are providing an unprecedented level of detail oncellular heterogeneity, offering new opportunities to decipher its functional role. In this review, wewill focus on three key aspects of early heart morphogenesis: First, the segregation of myocardial andendocardial lineages, which yields an early lineage diversification in cardiac development; second,the signaling cues driving differentiation in these progenitor cells; and third, the transcriptionalheterogeneity of cardiomyocyte progenitors of the primitive heart tube. Finally, we discuss howsingle-cell transcriptomics and epigenomics, together with live imaging and functional analyses, willlikely transform the way we delve into the complexity of cardiac development and its links withcongenital defects.

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