scholarly journals β3-Adrenoreceptors Control Mitochondrial Dormancy in Melanoma and Embryonic Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Maura Calvani ◽  
Lorenzo Cavallini ◽  
Annalisa Tondo ◽  
Valentina Spinelli ◽  
Luisa Ricci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Aerobic Glycolysis ◽  
Uncoupling Protein ◽  
Embryonic Stem ◽  
Atp Synthesis ◽  
Early Embryo ◽  
Mitochondrial Activity ◽  
Metabolic Switch ◽  
Cancer Cell Survival

The early phases of embryonic development and cancer share similar strategies to improve their survival in an inhospitable environment: both proliferate in a hypoxic and catecholamine-rich context, increasing aerobic glycolysis. Recent studies show that β3-adrenergic receptor (β3-AR) is involved in tumor progression, playing an important role in metastasis. Among β-adrenergic receptors, β3-AR is the last identified member of this family, and it is involved in cancer cell survival and induction of stromal reactivity in the tumor microenvironment. β3-AR is well known as a strong activator of uncoupling protein 1 (UCP1) in brown fat tissue. Interestingly, β3-AR is strongly expressed in early embryo development and in many cancer tissues. Induction of uncoupling protein 2 (UCP2) has been related to cancer metabolic switch, leading to accelerated glycolysis and reduced mitochondrial activity. In this study, for the first time, we demonstrate that β3-AR is able to promote this metabolic shift in both cancer and embryonic stem cells, inducing specific glycolytic cytoplasmic enzymes and a sort of mitochondrial dormancy through the induction of UCP2. The β3-AR/UCP2 axis induces a strong reduction of mitochondrial activity by reducing ATP synthesis and mitochondrial reactive oxygen species (mtROS) content. These effects are reverted by SR59230A, the specific β3-AR antagonist, causing an increase in mtROS. The increased level of mtROS is neutralized by a strong antioxidant activity in embryonic stem cells, but not in cancer stem cells, where it causes a dramatic reduction in tumor cell viability. These results lead to the possibility of a selective antitumor therapeutic use of SR59230A. Notably, we demonstrate the presence of β3-AR within the mitochondrial membrane in both cell lines, leading to the control of mitochondrial dormancy.

scholarly journals Mechanism of PKA-Dependent and Lipid-Raft Independent Stimulation of Connexin43 Expression by Oxytoxin in Mouse Embryonic Stem Cells

2012 ◽  
Vol 26 (7) ◽  
pp. 1144-1157 ◽  
Author(s):  
Seung Pil Yun ◽  
Su Shin Park ◽  
Jung Min Ryu ◽  
Jae Hong Park ◽  
Mi Ok Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Lipid Raft ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Creb Binding Protein ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression

Abstract Previous studies shows that connexins appear very early during murine embryo development, the gap junctional intercellular communication found in the inner cell mass of early embryo is also maintained in embryonic stem cells (ESC), and expression of oxytocin receptor (OTR) is developmentally regulated at early embryonic development. However, effect of oxytocin (OT) on the regulation of the connexin43 (Cx43) and maintenance of undifferentiation is not fully understood in stem cells. Therefore, we investigated the effect of OT on Cx43 expression and related signaling cascades in mouse ESC. OT increased Cx43 expression that was inhibited by the OTR inhibitor atosiban. In experiments to examine whether the effect of OT depends on lipid rafts, caveolin-1 (cav-1), cav-2, and flotillin-2, but not OTR, were detected in lipid raft fractions. Also, colocalization of OTR, cav-1, and cav-2 was not detected. Moreover, the lipid raft disruptor methyl-β-cyclodextrin did not attenuate OT-induced Cx43 expression. In experiments to examine related signaling pathways, OT activated cAMP/protein kinase A (PKA) which was inhibited by adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor PKI. OT increased nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) phosphorylation which was inhibited by PKI. OT also increased cAMP response element-binding (CREB)/CREB-binding protein (CBP) expression in the nucleus and induced the formation of CREB1/NF-κB/CBP complexes, which was blocked by the NF-κB-specific small interfering RNA, NF-κB inhibitors, SN50, and bay11–7082. Complex disruption by NF-κB inhibitors decreased OT-induced Cx43 expression. In conclusion, OT stimulates Cx43 expression through the NF-κB/CREB/CBP complex via the lipid raft-independent OTR-mediated cAMP/PKA in mouse ESC.

The Role of Mitochondrial Activity in the Differentiation of Human Embryonic Stem Cells (ESCs)

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Glenn Marsboom ◽  
Jonathan Paul ◽  
Peter T. Toth ◽  
Yanmin Zhang ◽  
Asrar B Malik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mitochondrial Activity

A novel NK-type homeobox gene, ENK (early embryo specific NK), preferentially expressed in embryonic stem cells

2003 ◽  
Vol 3 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Sue-Hong Wang ◽  
Ming-Shiun Tsai ◽  
Ming-Fu Chiang ◽  
Hung Li
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Homeobox Gene ◽  
Early Embryo

scholarly journals DPPA2 and DPPA4 are necessary to establish a totipotent state in mouse embryonic stem cells

2018 ◽  
Author(s):  
Alberto De Iaco ◽  
Alexandre Coudray ◽  
Julien Duc ◽  
Didier Trono
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Cell Stage ◽  
Oocyte Expression ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAfter fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Here we identify the paralog proteins DPPA2 and DPPA4 as responsible for this process.

scholarly journals A reduction in ATP demand and mitochondrial activity with neural differentiation of human embryonic stem cells

2011 ◽  
Vol 124 (3) ◽  
pp. 348-358 ◽  
Author(s):  
M. J. Birket ◽  
A. L. Orr ◽  
A. A. Gerencser ◽  
D. T. Madden ◽  
C. Vitelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
Mitochondrial Activity

scholarly journals Identification of a new gene family specifically expressed in chicken embryonic stem cells and early embryo

2001 ◽  
Vol 103 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Hervé Acloque ◽  
Valérie Risson ◽  
Anne-Marie Birot ◽  
Riyota Kunita ◽  
Bertrand Pain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Gene Family ◽  
Embryonic Stem ◽  
Early Embryo ◽  
New Gene ◽  
Chicken Embryonic Stem Cells

scholarly journals Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Piya Prajumwongs ◽  
Oratai Weeranantanapan ◽  
Thiranut Jaroonwitchawan ◽  
Parinya Noisa
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Neural Development ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Neural Induction ◽  
Early Embryo ◽  
Species Specific

Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo developmentin vivoat certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

scholarly journals Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kentaro Mochizuki ◽  
Jafar Sharif ◽  
Kenjiro Shirane ◽  
Kousuke Uranishi ◽  
Aaron B. Bogutz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Dna Binding ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Germline Genes ◽  
Post Implantation

AbstractSilencing of a subset of germline genes is dependent upon DNA methylation (DNAme) post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Indeed, in embryonic stem cells (ESCs), an overlapping set of genes, including germline “genome-defence” (GGD) genes, are upregulated following deletion of the H3K9 methyltransferase SETDB1 or subunits of the non-canonical PRC1 complex PRC1.6. Here, we show that in pre-implantation embryos and naïve ESCs (nESCs), hypomethylated promoters of germline genes bound by the PRC1.6 DNA-binding subunits MGA/MAX/E2F6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes in nESCs shows a greater dependence on PRC1.6 than DNAme. In contrast, GGD genes are hypermethylated in epiblast-like cells (EpiLCs) and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNAme, with H3K9me3 and DNAme establishment dependent upon MGA binding. Thus, GGD genes are initially repressed by PRC1.6, with DNAme subsequently engaged in post-implantation embryos.

scholarly journals 3D synthetic microscaffolds promote homogenous expression of NANOG in mouse embryonic stem cells

2020 ◽  
Author(s):  
Natalia A. Bakhtina ◽  
Madlen Müller ◽  
Harry Wischnewski ◽  
Rajika Arora ◽  
Constance Ciaudo
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Cell Communication ◽  
Early Embryo ◽  
Pluripotency Factors ◽  
Physiological Relevance ◽  
Synthetic Scaffold

The development of in vitro models, which accurately recapitulate early embryonic development, is one of the fundamental challenges in stem cell research. Most of the currently employed approaches involve the culture of embryonic stem cells (ESCs) on two-dimensional (2D) surfaces. However, the monolayer nature of these cultures does not permit cells to grow and proliferate in realistic three-dimensional (3D) microenvironments, as in an early embryo. In this paper, novel 3D synthetic scaffold arrays, fabricated by two-photon polymerization photolithography, are utilized to mimic tissue-specific architecture, enabling cell-to-matrix interaction and cell-to-cell communication in vitro. Mouse ESCs (mESCs) are able to grow and proliferate on these structures and maintain their pluripotent state. Furthermore, the 3D microscaffold arrays are integrated into a microscopy slide allowing the evaluation of the expression of key pluripotency factors at the single-cell level. Comparing 2D and 3D surfaces, mESCs grown in serum+LIF on 3D microscaffolds exhibit a stronger and more homogenous expression of NANOG and OCT4 pluripotency factors, than cells cultivated in 2i media, demonstrating that 3D microscaffolds capture naive pluripotency in vitro. Thus, the slide affords a novel and unique tool to model and study mammalian early development with greater physiological relevance than conventional 2D cultures.

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