G-protein Coupled Receptors in Stem Cell Self-Renewal and Differentiation

Kobayashi, Nao; Hawes, Susan Melanie; Crook, Jeremy Micah; Pébay, Alice

doi:10.1007/s12015-010-9167-9

Cited by 24 publications

(15 citation statements)

References 235 publications

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“…Microarray and gene ontology analysis shows that miR-153 over-expression repressed cell-signaling pathways including GPCR pathways, which are important for NSC maturation (Callihan et al, 2011; Kobayashi et al, 2010). Collectively, repressed ontology categories were broadly associated with mature neural function, suggesting that miR-153 served as a repressor of neuronal differentiation in NSCs.…”

Section: Discussionmentioning

confidence: 99%

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

et al. 2014

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Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

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Section: Discussionmentioning

confidence: 99%

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

et al. 2014

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“…The function ascribed to GPCRs is the result of agonist binding to the receptor, resulting in activation of specific G proteins such as stimulatory Gαs and inhibitory Gαi subunits, which selectively activate or inactivate effector pathways to mediate the desired responses (Kobilka, 2007, Wess, 1997). However, little is known about the role of GPCRs in mediating the differentiation of stem cells to terminally differentiated cells (Callihan et al., 2011, Kobayashi et al., 2010). To date, work has centered on pathways in adult stem cells such as signals emanating from specialized GPCRs (Frizzled proteins) of the WNT pathway and chemokine receptors such as CXCR4 expressed in stem cells (Holland et al., 2013, Van Camp et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

PAR1 Scaffolds TGFβRII to Downregulate TGF-β Signaling and Activate ESC Differentiation to Endothelial Cells

Gong

Sassmann

et al. 2016

Stem Cell Reports

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SummaryWe studied the function of the G-protein-coupled receptor PAR1 in mediating the differentiation of mouse embryonic stem cells (mESCs) to endothelial cells (ECs) that are capable of inducing neovascularization. We observed that either deletion or activation of PAR1 suppressed mouse embryonic stem cell (mESC) differentiation to ECs and neovascularization in mice. This was mediated by induction of TGFβRII/TGFβRI interaction, forming an active complex, which in turn induced SMAD2 phosphorylation. Inhibition of TGF-β signaling in PAR1-deficient mESCs restored the EC differentiation potential of mESCs. Thus, PAR1 in its inactive unligated state functions as a scaffold for TGFβRII to downregulate TGF-β signaling, and thereby promote ESC transition to functional ECs. The PAR1 scaffold function in ESCs is an essential mechanism for dampening TGF-β signaling and regulating ESC differentiation.

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“…These receptors control a large variety of key biological functions ranging from development, neurotransmission, secretion from endocrine and exocrine glands, inflammatory responses, blood pressure control, hemostasis, and cardiac function to name but a few (Dorsam and Gutkind, 2007; Pierce et al, 2002). GPCRs can also control fate decisions of stem cell progenitors during development (Knox et al, 2010; Kobayashi et al, 2010), and normal and tumor cell growth (Dorsam and Gutkind, 2007; Pierce et al, 2002; Rozengurt, 2007). Indeed, many potent mitogens including polypeptides (i.e., gastrin releasing peptide (GRP), endothelin, bradykinin, and angiotensin II), proteolytic enzymes (i.e., thrombin), chemokines (i.e., SDF-1), lipid mediators (i.e., prostaglandins, lysophospatidic acid (LPA) and sphingosine 1-phosphate (S1P)), and neurotransmitters (i.e., acetylcholine and noradrenaline), can promote cell proliferation by activating their cognate G protein-linked receptors in a variety of cells types (reviewed in (Dorsam and Gutkind, 2007; Rozengurt, 2007).…”

Section: Introductionmentioning

confidence: 99%

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

et al. 2013

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Activating mutations in GNAQ and GNA11, encoding members of the Gαq family of G protein α subunits, are the driver uveal melanoma oncogenes, while mutations in Gq-linked G proteincoupled receptors (GPCRs) have been identified recently in numerous human malignancies. How Gαq and its coupled receptors transduce mitogenic signals is still unclear, due to the complexity of signaling events perturbed upon Gq activation. Using of a synthetic biology approach and a genome-wide RNAi screen, we found that a highly conserved guanine nucleotide exchange factor, Trio, is essential to activate Rho- and Rac-regulated signaling pathways acting on JNK and p38, thereby transducing proliferative signals from Gαq to the nucleus independently of PLC-β. Indeed, while many biological responses elicited by Gq depend on the transient activation of second messenger system, Gq utilizes a hardwired protein-protein interaction-based signaling circuitry to achieve the sustained stimulation of proliferative pathways, thereby controlling normal and aberrant cell growth.

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G-protein Coupled Receptors in Stem Cell Self-Renewal and Differentiation

Cited by 24 publications

References 235 publications

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

PAR1 Scaffolds TGFβRII to Downregulate TGF-β Signaling and Activate ESC Differentiation to Endothelial Cells

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

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