scholarly journals Nodal mutant eXtraembryonic ENdoderm (XEN) stem cells upregulate markers for the anterior visceral endoderm and impact the timing of cardiac differentiation in mouse embryoid bodies

Biology Open ◽  
2012 ◽  
Vol 1 (3) ◽  
pp. 208-219 ◽  
Author(s):  
W. Liu ◽  
K. Brown ◽  
S. Legros ◽  
A. C. Foley
Keyword(s):  
Stem Cells ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Visceral Endoderm ◽  
Extraembryonic Endoderm ◽  
Anterior Visceral Endoderm

scholarly journals Mitochondrial Fusion by M1 Promotes Embryoid Body Cardiac Differentiation of Human Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jarmon G. Lees ◽  
Anne M. Kong ◽  
Yi C. Chen ◽  
Priyadharshini Sivakumaran ◽  
Damián Hernández ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryoid Body ◽  
Mitochondrial Dynamics ◽  
Embryoid Bodies ◽  
Mitochondrial Fusion ◽  
Cardiac Differentiation ◽  
Patient Specific ◽  
Mitochondrial Morphology ◽  
Human Ipscs

Human induced pluripotent stem cells (iPSCs) can be differentiated in vitro into bona fide cardiomyocytes for disease modelling and personalized medicine. Mitochondrial morphology and metabolism change dramatically as iPSCs differentiate into mesodermal cardiac lineages. Inhibiting mitochondrial fission has been shown to promote cardiac differentiation of iPSCs. However, the effect of hydrazone M1, a small molecule that promotes mitochondrial fusion, on cardiac mesodermal commitment of human iPSCs is unknown. Here, we demonstrate that treatment with M1 promoted mitochondrial fusion in human iPSCs. Treatment of iPSCs with M1 during embryoid body formation significantly increased the percentage of beating embryoid bodies and expression of cardiac-specific genes. The pro-fusion and pro-cardiogenic effects of M1 were not associated with changes in expression of the α and β subunits of adenosine triphosphate (ATP) synthase. Our findings demonstrate for the first time that hydrazone M1 is capable of promoting cardiac differentiation of human iPSCs, highlighting the important role of mitochondrial dynamics in cardiac mesoderm lineage specification and cardiac development. M1 and other mitochondrial fusion promoters emerge as promising molecular targets to generate lineages of the heart from human iPSCs for patient-specific regenerative medicine.

scholarly journals Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Damián Hernández ◽  
Rodney Millard ◽  
Priyadharshini Sivakumaran ◽  
Raymond C. B. Wong ◽  
Duncan E. Crombie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Electrical Stimulation ◽  
Induced Pluripotent Stem Cells ◽  
Cell Line ◽  
Pluripotent Stem Cells ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Dependent Manner ◽  
Human Ipscs ◽  
Induced Pluripotent

Background.Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes.Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days.Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression ofACTC1,TNNT2,MYH7, andMYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner.Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

scholarly journals High density cultures of embryoid bodies enhanced cardiac differentiation of murine embryonic stem cells

2011 ◽  
Vol 416 (1-2) ◽  
pp. 51-57 ◽  
Author(s):  
Min Young Lee ◽  
Esra Cagavi Bozkulak ◽  
Simon Schliffke ◽  
Peter J. Amos ◽  
Yongming Ren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
High Density ◽  
Cardiac Differentiation ◽  
Murine Embryonic Stem Cells

Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4795-4805 ◽  
Author(s):  
E. Barbacci ◽  
M. Reber ◽  
M.O. Ott ◽  
C. Breillat ◽  
F. Huetz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Embryoid Bodies ◽  
Nuclear Factor ◽  
Visceral Endoderm ◽  
Hepatocyte Nuclear Factor ◽  
Parietal Endoderm ◽  
Nuclear Factor 1

Genetic and molecular evidence indicates that visceral endoderm, an extraembryonic cell lineage, is required for gastrulation, early anterior neural patterning, cell death and specification of posterior mesodermal cell fates. We show that variant Hepatocyte Nuclear Factor 1 (vHNF1), a homeodomain-containing transcription factor first expressed in the primitive endoderm, is required for the specification of visceral endoderm. vHnf1-deficient mouse embryos develop normally to the blastocyst stage, start implantation, but die soon afterwards, with abnormal or absent extraembryonic region, poorly organised ectoderm and no discernible visceral or parietal endoderm. However, immunostaining analysis of E5.5 nullizygous mutant embryos revealed the presence of parietal endoderm-like cells lying on an abnormal basal membrane. Homozygous mutant blastocyst outgrowths or differentiated embryonic stem cells do not express early or late visceral endoderm markers. In addition, in vHnf1 null embryoid bodies there is no activation of the transcription factors HNF-4alpha1, HNF1alpha and HNF-3gamma. Aggregation of vHnf1-deficient embryonic stem cells with wild-type tetraploid embryos, which contribute exclusively to extraembryonic tissues, rescues periimplantation lethality and allows development to progress to early organogenesis. Our results place vHNF1 in a preeminent position in the regulatory network that specifies the visceral endoderm and highlight the importance of this cell lineage for proper growth and differentiation of primitive ectoderm in pregastrulating embryos.

scholarly journals Basal-type lumenogenesis in extraembryonic endoderm stem cells models the early visceral endoderm

2019 ◽  
Vol 132 (19) ◽  
pp. jcs230607 ◽  
Author(s):  
Minjae Kim ◽  
Yixiang Zhong ◽  
Kyoung Hwa Jung ◽  
Young Gyu Chai ◽  
Bert Binas
Keyword(s):  
Stem Cells ◽  
Visceral Endoderm ◽  
Extraembryonic Endoderm ◽  
Basal Type

scholarly journals Nitro-Oleic Acid Inhibits Stemness Maintenance and Enhances Neural Differentiation of Mouse Embryonic Stem Cells via STAT3 Signaling

2021 ◽  
Vol 22 (18) ◽  
pp. 9981
Author(s):  
Jana Pereckova ◽  
Michaela Pekarova ◽  
Nikoletta Szamecova ◽  
Zuzana Hoferova ◽  
Kristyna Kamarytova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Oleic Acid ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Class Iii ◽  
Stat3 Phosphorylation ◽  
Stem Cell Pluripotency

Nitro-oleic acid (NO2-OA), pluripotent cell-signaling mediator, was recently described as a modulator of the signal transducer and activator of transcription 3 (STAT3) activity. In our study, we discovered new aspects of NO2-OA involvement in the regulation of stem cell pluripotency and differentiation. Murine embryonic stem cells (mESC) or mESC-derived embryoid bodies (EBs) were exposed to NO2-OA or oleic acid (OA) for selected time periods. Our results showed that NO2-OA but not OA caused the loss of pluripotency of mESC cultivated in leukemia inhibitory factor (LIF) rich medium via the decrease of pluripotency markers (NANOG, sex-determining region Y-box 1 transcription factor (SOX2), and octamer-binding transcription factor 4 (OCT4)). The effects of NO2-OA on mESC correlated with reduced phosphorylation of STAT3. Subsequent differentiation led to an increase of the ectodermal marker orthodenticle homolog 2 (Otx2). Similarly, treatment of mESC-derived EBs by NO2-OA resulted in the up-regulation of both neural markers Nestin and β-Tubulin class III (Tubb3). Interestingly, the expression of cardiac-specific genes and beating of EBs were significantly decreased. In conclusion, NO2-OA is able to modulate pluripotency of mESC via the regulation of STAT3 phosphorylation. Further, it attenuates cardiac differentiation on the one hand, and on the other hand, it directs mESC into neural fate.

scholarly journals Activin A Modulates CRIPTO-1/HNF4α+ Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Robin Duelen ◽  
Guillaume Gilbert ◽  
Abdulsamie Patel ◽  
Nathalie de Schaetzen ◽  
Liesbeth De Waele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Heart Development ◽  
Embryoid Body ◽  
Embryonic Stem ◽  
Activin A ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Potential Applications

The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation. Addition of high levels of Activin A during embryoid body cardiac differentiation augmented the generation of endoderm derivatives, which in turn promoted cardiomyocyte differentiation. Moreover, a dose-dependent increase in the coreceptor expression of the TGF-β superfamily member CRIPTO-1 was observed in response to Activin A. We hypothesized that interactions between cells derived from meso- and endodermal lineages in embryoid bodies contributed to improved cell maturation in early stages of cardiac differentiation, improving the beating frequency and the percentage of contracting embryoid bodies. Activin A did not seem to affect the properties of cardiomyocytes at later stages of differentiation, measuring action potentials, and intracellular Ca2+ dynamics. These findings are relevant for improving our understanding on human heart development, and the proposed protocol could be further explored to obtain cardiomyocytes with functional phenotypes, similar to those observed in adult cardiac myocytes.

scholarly journals Cardiopoietic programming of embryonic stem cells for tumor-free heart repair

2007 ◽  
Vol 204 (2) ◽  
pp. 405-420 ◽  
Author(s):  
Atta Behfar ◽  
Carmen Perez-Terzic ◽  
Randolph S. Faustino ◽  
D. Kent Arrell ◽  
Denice M. Hodgson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Nuclear Translocation ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Cardiac Progenitors ◽  
Tnf Α

Embryonic stem cells have the distinct potential for tissue regeneration, including cardiac repair. Their propensity for multilineage differentiation carries, however, the liability of neoplastic growth, impeding therapeutic application. Here, the tumorigenic threat associated with embryonic stem cell transplantation was suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-α, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF-α to promote cardiac differentiation was recapitulated in embryoid bodies in vitro. The procardiogenic action required an intact endoderm and was mediated by secreted cardio-inductive signals. Resolved TNF-α–induced endoderm-derived factors, combined in a cocktail, secured guided differentiation of embryonic stem cells in monolayers produce cardiac progenitors termed cardiopoietic cells. Characterized by a down-regulation of oncogenic markers, up-regulation, and nuclear translocation of cardiac transcription factors, this predetermined population yielded functional cardiomyocyte progeny. Recruited cardiopoietic cells delivered in infarcted hearts generated cardiomyocytes that proliferated into scar tissue, integrating with host myocardium for tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone stem cell pluripotency, offering a tumor-resistant approach for regeneration.

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