scholarly journals SR9009 has REV-ERB–independent effects on cell proliferation and metabolism

2019 ◽  
Vol 116 (25) ◽  
pp. 12147-12152 ◽  
Author(s):  
Pieterjan Dierickx ◽  
Matthew J. Emmett ◽  
Chunjie Jiang ◽  
Kahealani Uehara ◽  
Manlu Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Nuclear Receptors ◽  
Embryonic Stem ◽  
Diseased Animal ◽  
Cell Systems ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Genetic Deletion ◽  
Independent Effects

The nuclear receptors REV-ERBα and -β link circadian rhythms and metabolism. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well as diseased animal models and cell systems. However, the direct involvement of REV-ERBs in these effects of SR9009 has not been thoroughly assessed, as experiments were not performed in the complete absence of both proteins. Here, we report the generation of a mouse model for conditional genetic deletion of REV-ERBα and -β. We show that SR9009 can decrease cell viability, rewire cellular metabolism, and alter gene transcription in hepatocytes and embryonic stem cells lacking both REV-ERBα and -β. Thus, the effects of SR9009 cannot be used solely as surrogate for REV-ERB activity.

scholarly journals PPARγ-dependent and PPARγ-independent effects on the development of adipose cells from embryonic stem cells

FEBS Letters ◽  
2001 ◽  
Vol 510 (1-2) ◽  
pp. 94-98 ◽  
Author(s):  
C. Vernochet ◽  
D.S. Milstone ◽  
C. Iehlé ◽  
N. Belmonte ◽  
B. Phillips ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Independent Effects ◽  
Adipose Cells

scholarly journals Thyroid Hormone Signaling in Embryonic Stem Cells: Crosstalk with the Retinoic Acid Pathway

2020 ◽  
Vol 21 (23) ◽  
pp. 8945
Author(s):  
Mercedes Fernández ◽  
Micaela Pannella ◽  
Vito Antonio Baldassarro ◽  
Alessandra Flagelli ◽  
Giuseppe Alastra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Embryonic Stem Cells ◽  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Postnatal Life ◽  
Gene And Protein Expression

While the role of thyroid hormones (THs) during fetal and postnatal life is well-established, their role at preimplantation and during blastocyst development remains unclear. In this study, we used an embryonic stem cell line isolated from rat (RESC) to study the effects of THs and retinoic acid (RA) on early embryonic development during the pre-implantation stage. The results showed that THs play an important role in the differentiation/maturation processes of cells obtained from embryoid bodies (EB), with thyroid hormone nuclear receptors (TR) (TRα and TRβ), metabolic enzymes (deiodinases 1, 2, 3) and membrane transporters (Monocarboxylate transporters -MCT- 8 and 10) being expressed throughout in vitro differentiation until the Embryoid body (EB) stage. Moreover, thyroid hormone receptor antagonist TR (1-850) impaired RA-induced neuroectodermal lineage specification. This effect was significantly higher when cells were treated with retinoic acid (RA) to induce neuroectodermal lineage, studied through the gene and protein expression of nestin, an undifferentiated progenitor marker from the neuroectoderm lineage, as established by nestin mRNA and protein regulation. These results demonstrate the contribution of the two nuclear receptors, TR and RA, to the process of neuroectoderm maturation of the in vitro model embryonic stem cells obtained from rat.

scholarly journals Expression Profiling of Nuclear Receptors in Human and Mouse Embryonic Stem Cells

2009 ◽  
Vol 23 (5) ◽  
pp. 724-733 ◽  
Author(s):  
Chang-Qing Xie ◽  
Yangsik Jeong ◽  
Mingui Fu ◽  
Angie L. Bookout ◽  
Minerva T. Garcia-Barrio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nuclear Receptors ◽  
Expression Profiling ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Human And Mouse

scholarly journals MicroRNA-302b-3p Suppresses Cell Proliferation Through AKT Pathway by Targeting IGF-1R in Human Gastric Cancer

2017 ◽  
Vol 42 (4) ◽  
pp. 1701-1711 ◽  
Author(s):  
Bo Guo ◽  
Zhenghao Zhao ◽  
Zhen Wang ◽  
Qian Li ◽  
Xiaofei Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Biological Effects ◽  
Embryonic Stem ◽  
Luciferase Reporter ◽  
Human Gastric Cancer ◽  
Cancer Tissues

Background/Aims: MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. Methods: Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p. Western blotting and RNA interference were used to evaluate the expression of the AKT signaling pathway and determine the mechanisms underlying miR-302b-3p-induced anti-tumor effects. Results: MiR-302b-3p expression was decreased in gastric cancer tissues and cell lines. Enforced expression of miR-302b suppressed cell proliferation and cell cycle G1-S transition and induced apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p overexpression in gastric cancer cells. Importantly, both overexpression of miR-302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and apoptotic protein Bax/Bcl-2. Conclusion: These results indicate the tumor suppressor role of miR-302b-3p in the pathogenesis of gastric cancer.

scholarly journals Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75697 ◽  
Author(s):  
Roger Kenneth Whealands Smith ◽  
Natalie Jayne Werling ◽  
Stephanie Georgina Dakin ◽  
Rafiqul Alam ◽  
Allen E. Goodship ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Autologous Bone Marrow ◽  
Beneficial Effects ◽  
Naturally Occurring ◽  
Autologous Bone

scholarly journals Evolutionarily Conserved Role of Nucleostemin: Controlling Proliferation of Stem/Progenitor Cells during Early Vertebrate Development

2006 ◽  
Vol 26 (24) ◽  
pp. 9291-9301 ◽  
Author(s):  
Chantal Beekman ◽  
Massimo Nichane ◽  
Sarah De Clercq ◽  
Marion Maetens ◽  
Thomas Floss ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Control Cell ◽  
Embryonic Stem ◽  
Physiological Role ◽  
Specific Gene

ABSTRACT Nucleostemin (NS) is a putative GTPase expressed preferentially in the nucleoli of neuronal and embryonic stem cells and several cancer cell lines. Transfection and knockdown studies indicated that NS controls the proliferation of these cells by interacting with the p53 tumor suppressor protein and regulating its activity. To assess the physiological role of NS in vivo, we generated a mutant mouse line with a specific gene trap event that inactivates the NS allele. The corresponding NS −/− embryos died around embryonic day 4. Analyses of NS mutant blastocysts indicated that NS is not required to maintain pluripotency, nucleolar integrity, or survival of the embryonic stem cells. However, the homozygous mutant blastocysts failed to enter S phase even in the absence of functional p53. Haploid insufficiency of NS in mouse embryonic fibroblasts leads to decreased cell proliferation. NS also functions in early amphibian development to control cell proliferation of neural progenitor cells. Our results show that NS has a unique ability, derived from an ancestral function, to control the proliferation rate of stem/progenitor cells in vivo independently of p53.

scholarly journals Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells

2020 ◽  
Author(s):  
Síle M. Griffin ◽  
Mark R. Pickard ◽  
Clive P. Hawkins ◽  
Adrian C. Williams ◽  
Rosemary A. Fricker
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Tyrosine Hydroxylase ◽  
Cell Cultures ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Progenitors ◽  
Neuronal Populations ◽  
Regenerative Therapies

AbstractEmerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action.Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2’-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression.These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.

Sign in / Sign up

Export Citation Format

Share Document