Model systems for the study of heart development and disease

2007 ◽  
Vol 18 (1) ◽  
pp. 1-2
Author(s):  
Robert A. Schulz ◽  
Brian L. Black
Keyword(s):  
Heart Development ◽  
Model Systems

scholarly journals Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells

2021 ◽  
Vol 22 (6) ◽  
pp. 3005
Author(s):  
Emma Claire James ◽  
Eva Tomaskovic-Crook ◽  
Jeremy Micah Crook
Keyword(s):  
Stem Cells ◽  
Heart Disease ◽  
Electric Fields ◽  
Pluripotent Stem Cells ◽  
Heart Development ◽  
Disease Patient ◽  
Toxicity Testing ◽  
Model Systems ◽  
Patient Specific ◽  
Cardiac Tissues

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.

scholarly journals Model system identification of novel congenital heart disease gene candidates: focus on RPL13

2019 ◽  
Vol 28 (23) ◽  
pp. 3954-3969 ◽  
Author(s):  
Analyne M Schroeder ◽  
Massoud Allahyari ◽  
Georg Vogler ◽  
Maria A Missinato ◽  
Tanja Nielsen ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Throughput ◽  
Heart Development ◽  
Congenital Heart ◽  
De Novo ◽  
Model Systems ◽  
New Genes ◽  
Cardiac Model

Abstract Genetics is a significant factor contributing to congenital heart disease (CHD), but our understanding of the genetic players and networks involved in CHD pathogenesis is limited. Here, we searched for de novo copy number variations (CNVs) in a cohort of 167 CHD patients to identify DNA segments containing potential pathogenic genes. Our search focused on new candidate disease genes within 19 deleted de novo CNVs, which did not cover known CHD genes. For this study, we developed an integrated high-throughput phenotypical platform to probe for defects in cardiogenesis and cardiac output in human induced pluripotent stem cell (iPSC)-derived multipotent cardiac progenitor (MCPs) cells and, in parallel, in the Drosophila in vivo heart model. Notably, knockdown (KD) in MCPs of RPL13, a ribosomal gene and SON, an RNA splicing cofactor, reduced proliferation and differentiation of cardiomyocytes, while increasing fibroblasts. In the fly, heart-specific RpL13 KD, predominantly at embryonic stages, resulted in a striking ‘no heart’ phenotype. KD of Son and Pdss2, among others, caused structural and functional defects, including reduced or abolished contractility, respectively. In summary, using a combination of human genetics and cardiac model systems, we identified new genes as candidates for causing human CHD, with particular emphasis on ribosomal genes, such as RPL13. This powerful, novel approach of combining cardiac phenotyping in human MCPs and in the in vivo Drosophila heart at high throughput will allow for testing large numbers of CHD candidates, based on patient genomic data, and for building upon existing genetic networks involved in heart development and disease.

scholarly journals Model systems for the study of heart development and disease

2007 ◽  
Vol 18 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Mary R. Hutson ◽  
Margaret L. Kirby
Keyword(s):  
Heart Development ◽  
Model Systems

The Ultrastructure of Myocardial Cells in Normal and Cardiac Lethal Mutant Mexican Axolotls, (Ambystoma Mexicanum)

1970 ◽  
Vol 28 ◽  
pp. 62-63
Author(s):  
Larry F. Lemanski ◽  
Eldridge M. Bertke ◽  
J. T. Justus
Keyword(s):  
Fine Structure ◽  
Heart Development ◽  
Osmium Tetroxide ◽  
Picric Acid ◽  
Ambystoma Mexicanum ◽  
Recessive Mutation ◽  
Acid Mixture ◽  
Myocardial Cells ◽  
Lethal Mutant ◽  
Mexican Axolotl

A recessive mutation has been recently described in the Mexican Axolotl, Ambystoma mexicanum; in which the heart forms structurally, but does not contract (Humphrey, 1968. Anat. Rec. 160:475). In this study, the fine structure of myocardial cells from normal (+/+; +/c) and cardiac lethal mutant (c/c) embryos at Harrison's stage 40 was compared. The hearts were fixed in a 0.1 M phosphate buffered formaldehyde-glutaraldehyde-picric acid-styphnic acid mixture and were post fixed in 0.1 M s-collidine buffered 1% osmium tetroxide. A detailed study of heart development in normal and mutant embryos from stages 25-46 will be described elsewhere.

Reversal of cardiomyopathy resulting from prenatal exposure to ethanol

1984 ◽  
Vol 42 ◽  
pp. 716-717
Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie
Keyword(s):  
Prenatal Exposure ◽  
Heart Development ◽  
Membrane Integrity ◽  
Ethanol Exposure ◽  
Prenatal Ethanol Exposure ◽  
Pathological Changes ◽  
Prenatally Exposed ◽  
Inner Mitochondrial Membrane ◽  
Fetal Alcohol ◽  
Newborn Mice

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.

Nuclear coiled bodies and the nucleolus

1994 ◽  
Vol 52 ◽  
pp. 20-21
Author(s):  
K. Brasch ◽  
J. Williams ◽  
D. Gallo ◽  
T. Lee ◽  
R. L. Ochs
Keyword(s):  
Mouse Liver ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Model Systems ◽  
Coiled Body ◽  
Rrna Processing ◽  
Malignant Cells ◽  
Sm Proteins ◽  
Coiled Bodies ◽  
Unique Protein

Though first described in 1903 by Ramon-y-Cajal as silver-staining “accessory bodies” to nucleoli, nuclear bodies were subsequently rediscovered by electron microscopy about 30 years ago. Nuclear bodies are ubiquitous, but seem most abundant in hyperactive and malignant cells. The best studied type of nuclear body is the coiled body (CB), so termed due to characteristic morphology and content of a unique protein, p80-coilin (Fig.1). While no specific functions have as yet been assigned to CBs, they contain spliceosome snRNAs and proteins, and also the nucleolar protein fibrillarin. In addition, there is mounting evidence that CBs arise from or are generated near the nucleolus and then migrate into the nucleoplasm. This suggests that as yet undefined links may exist, between nucleolar pre-rRNA processing events and the spliceosome-associated Sm proteins in CBs.We are examining CB and nucleolar changes in three diverse model systems: (1) estrogen stimulated chick liver, (2) normal and neoplastic cells, and (3) polyploid mouse liver.

Microtubule Dynamics and Organelle Transport in Reticulomyxa

1990 ◽  
Vol 48 (3) ◽  
pp. 194-195
Author(s):  
Yih-Tai Chen ◽  
Ursula Euteneuer ◽  
Ken B. Johnson ◽  
Michael P. Koonce ◽  
Manfred Schliwa
Keyword(s):  
Plasma Membrane ◽  
Light Microscopy ◽  
Cytoplasmic Dynein ◽  
Living Cells ◽  
Microtubule Dynamics ◽  
Model Systems ◽  
Organelle Transport ◽  
Biochemical Characteristics ◽  
Dependent Transport

The application of video techniques to light microscopy and the development of motility assays in reactivated or reconstituted model systems rapidly advanced our understanding of the mechanism of organelle transport and microtubule dynamics in living cells. Two microtubule-based motors have been identified that are good candidates for motors that drive organelle transport: kinesin, a plus end-directed motor, and cytoplasmic dynein, which is minus end-directed. However, the evidence that they do in fact function as organelle motors is still indirect.We are studying microtubule-dependent transport and dynamics in the giant amoeba, Reticulomyxa. This cell extends filamentous strands backed by an extensive array of microtubules along which organelles move bidirectionally at up to 20 μm/sec (Fig. 1). Following removal of the plasma membrane with a mild detergent, organelle transport can be reactivated by the addition of ATP (1). The physiological, pharmacological and biochemical characteristics show the motor to be a cytoplasmic form of dynein (2).

Microstructural observations of the “Wustite-Spinel” coexistence following quenching of cation-excess spinels, Ni2(1+x)Ti1-xO4

1990 ◽  
Vol 48 (4) ◽  
pp. 1058-1059
Author(s):  
Ian M. Anderson ◽  
Arnulf Muan ◽  
C. Barry Carter
Keyword(s):  
Film Growth ◽  
Spinel Phase ◽  
Model Systems ◽  
Ion Milling ◽  
Coexistence Of Phases ◽  
Nonequilibrium Conditions ◽  
Diffraction Patterns ◽  
Spinel Structures ◽  
Highly Porous ◽  
Standard Techniques

Oxide mixtures which feature a coexistence of phases with the wüstite and spinel structures are considered model systems for the study of solid-state reaction kinetics, phase boundaries, and thin-film growth, and such systems are especially suited to TEM studies. (In this paper, the terms “wüstite” and “spinel” will refer to phases of those structure types.) The study of wüstite-spinel coexistence has been limited mostly to systems near their equilibrium condition, where the assumptions of local thermodynamic equilibrium are valid. The cation-excess spinels of the type Ni2(1+x)Ti1-xO4, which reportedly exist only above 1375°C4, provide an excellent system for the study of wüstite-spinel coexistence under highly nonequilibrium conditions. The nature of these compounds has been debated in the literature. X-ray and neutron powder diffraction patterns have been used to advocate the existence of a single-phase, non- stoichiometric spinel. TEM studies of the microstructure have been used to suggest equilibrium coexistence of a stoichiometric spinel, Ni2TiO4, and a wüstite phase; this latter study has shown a coexistence of wüstite and spinel phases in specimens thought to have been composed of a single, non- stoichiometric spinel phase. The microstructure and nature of this phase coexistence is the focus of this study. Specimens were prepared by ball-milling a mixture of NiO and TiO2 powders with 10 wt.% TiO2. The mixture was fired in air at 1483°C for 5 days, and then quenched to room temperature. The aggregate thus produced was highly porous, and needed to be infiltrated prior to TEM sample preparation, which was performed using the standard techniques of lapping, dimpling, and ion milling.

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