The Experts below are selected from a list of 161097096 Experts worldwide ranked by ideXlab platform
Jiuhong Kang - One of the best experts on this subject based on the ideXlab platform.
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the mir 590 ACVR2A terf1 axis regulates telomere elongation and pluripotency of mouse ipscs
Stem cell reports, 2018Co-Authors: Qidong Liu, Guiying Wang, Yao Lyu, Mingliang Bai, Zeyidan Jiapaer, Wenwen Jia, Tong Han, Rong Weng, Yiwei Yang, Jiuhong KangAbstract:During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (ACVR2A) is the downstream target and mediates the function of miR-590. Downregulation of ACVR2A promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shACVR2A-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs.
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a mir 590 ACVR2A rad51b axis regulates dna damage repair during mesc proliferation
Stem cell reports, 2014Co-Authors: Qidong Liu, Guiying Wang, Yafang Chen, Dandan Yang, Jiuhong KangAbstract:Embryonic stem cells (ESCs) enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF), which maintains the self-renewal capability of mouse ESCs (mESCs), significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB) and double-strand break (DSB) damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (ACVR2A) to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR) gene, Rad51b, as a downstream molecule of the miR-590/ACVR2A pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/ACVR2A/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.
Qidong Liu - One of the best experts on this subject based on the ideXlab platform.
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the mir 590 ACVR2A terf1 axis regulates telomere elongation and pluripotency of mouse ipscs
Stem cell reports, 2018Co-Authors: Qidong Liu, Guiying Wang, Yao Lyu, Mingliang Bai, Zeyidan Jiapaer, Wenwen Jia, Tong Han, Rong Weng, Yiwei Yang, Jiuhong KangAbstract:During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (ACVR2A) is the downstream target and mediates the function of miR-590. Downregulation of ACVR2A promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shACVR2A-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs.
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The miR-590/ACVR2A/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs
'Elsevier BV', 2018Co-Authors: Qidong Liu, Guiying Wang, Yao Lyu, Mingliang Bai, Zeyidan Jiapaer, Wenwen Jia, Tong Han, Rong Weng, Yiwei YangAbstract:Summary: During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (ACVR2A) is the downstream target and mediates the function of miR-590. Downregulation of ACVR2A promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shACVR2A-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. : In this article, Kang and colleagues elucidate the critical function and regulatory mechanism of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. These findings not only determined the miR-590/ACVR2A/Terf1 axis on regulating both telomere elongation and pluripotency but also revealed an underlying mechanism pushing forward the maturation of the pre-iPSCs. Keywords: miR-590, ACVR2A, Terf1, iPSCs, pluripotency, telomer
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a mir 590 ACVR2A rad51b axis regulates dna damage repair during mesc proliferation
Stem cell reports, 2014Co-Authors: Qidong Liu, Guiying Wang, Yafang Chen, Dandan Yang, Jiuhong KangAbstract:Embryonic stem cells (ESCs) enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF), which maintains the self-renewal capability of mouse ESCs (mESCs), significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB) and double-strand break (DSB) damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (ACVR2A) to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR) gene, Rad51b, as a downstream molecule of the miR-590/ACVR2A pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/ACVR2A/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.
Daniel J Bernard - One of the best experts on this subject based on the ideXlab platform.
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murine fsh production depends on the activin type ii receptors ACVR2A and acvr2b
Endocrinology, 2020Co-Authors: Gauthier Schang, Hailey Schultz, Emilie Brule, Luisina Ongaro, Ulrich Boehm, Ying Wang, Xiang Zhou, Daniel J BernardAbstract:: Activins are selective regulators of follicle-stimulating hormone (FSH) production by pituitary gonadotrope cells. In a gonadotrope-like cell line, LβT2, activins stimulate FSH via the activin type IIA receptor (ACVR2A) and/or bone morphogenetic protein type II receptor (BMPR2). Consistent with these observations, FSH is greatly reduced, though still present, in global ACVR2A knockout mice. In contrast, FSH production is unaltered in gonadotrope-specific Bmpr2 knockout mice. In light of these results, we questioned whether an additional type II receptor might mediate the actions of activins or related TGFβ ligands in gonadotropes. We focused on the activin type IIB receptor (ACVR2B), even though it does not mediate activin actions in the gonadotrope-like cell line. Using a Cre-lox strategy, we ablated ACVR2A and/or Acvr2b in murine gonadotropes. The resulting conditional knockout (cKO) animals were compared to littermate controls. ACVR2A cKO (cKO-A) females were subfertile (~70% reduced litter size), cKO-A males were hypogonadal, and both sexes showed marked decreases in serum FSH levels compared to controls. Acvr2b cKO (cKO-B) females were subfertile (~20% reduced litter size), cKO-B males had a moderate decrease in testicular weight, but only males showed a significant decrease in serum FSH levels relative to controls. Simultaneous deletion of both ACVR2A and Acvr2b in gonadotropes led to profound hypogonadism and FSH deficiency in both sexes; females were acyclic and sterile. Collectively, these data demonstrate that ACVR2A and ACVR2B are the critical type II receptors through which activins or related TGFβ ligands induce FSH production in mice in vivo.
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Activins bind and signal via bone morphogenetic protein receptor type II (BMPR2) in immortalized gonadotrope-like cells
Cellular signalling, 2013Co-Authors: Carlis Rejon, Terence E. Hébert, Mark A. Hancock, Thomas B. Thompson, Daniel J BernardAbstract:TGFβ superfamily ligands greatly outnumber their receptors. Thus, receptors are shared between ligands and individual ligands can bind multiple receptors. Bone morphogenetic proteins (BMPs) bind and signal via both BMP type II (BMPR2) and activin type II (ACVR2) receptors. We hypothesized that, in addition to its canonical receptor ACVR2, activin A might similarly bind and signal via BMPR2. First, using surface plasmon resonance, we showed that activin A binds to the BMPR2 extracellular domain (ECD), though with lower affinity compared to the ACVR2-ECD. We confirmed these results in cells, where radiolabeled activin A bound to ACVR2 and BMPR2, but not to other type II receptors (AMHR2 or TGFBR2). Using homology modeling and site-directed mutagenesis, we identified key residues in BMPR2 that mediate its interaction with activin A. The soluble ECDs of ACVR2 or BMPR2 dose-dependently inhibited activin A-, but not TGFβ-induced signaling in cells, suggesting that activin binding to BMPR2 could have functional consequences. To address this idea, we altered BMPR2 expression levels in immortalized murine gonadotrope-like cells, LβT2, in which activins potently stimulate follicle-stimulating hormone β (Fshb) subunit transcription. BMPR2 expression potentiated activin A responses whereas depletion of endogenous BMPR2 with short interfering RNAs attenuated activin A-stimulated Fshb transcription. Additional data suggest, for the first time, that BMPR2 may form functional complexes with the canonical activin type I receptor, activin receptor-like kinase 4. Collectively, our data show that BMPR2, along with ACVR2, functions as a bona fide activin type II receptor in gonadotrope-like cells, thereby broadening our understanding of mechanisms of activin action.
Sanford D Markowitz - One of the best experts on this subject based on the ideXlab platform.
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evidence of selection for clones having genetic inactivation of the activin a type ii receptor acvr2 gene in gastrointestinal cancers
Cancer Research, 2003Co-Authors: Paula M Hempen, Ravi K Bansal, Kathleen M Murphy, Robert H Whitehead, Anirban Maitra, Christine A Iacobuziodonahue, Bert Vogelstein, Lin Zhang, Sanford D MarkowitzAbstract:The activin signaling pathway parallels the transforming growth factor (TGF)-β pathway. Both use extracellular ligands and cell surface receptors that are structurally and functionally related, as well as the same intracellular mediators (SMADs 2–4) to transmit these signals. Members of both pathways have been characterized previously as tumor suppressor genes on the demonstration of inactivating mutations in human neoplasms, e.g., genetic inactivation of the activin type I receptor was reported recently in pancreatic cancer. Here, we present evidence of selection for mutations of the activin A type II receptor (ACVR2) gene during human gastrointestinal carcinogenesis. Two 8-bp polyadenine tracts of the ACVR2 gene are targets for inactivating frameshift mutations in gastrointestinal neoplasms having microsatellite instability (MSI). These mutations are similar to those of the 10-bp polyadenine tract within the TGF-β type II receptor (TGFBR2), a well-characterized target of frameshift mutations in the same neoplasms. We identified biallelic mutations of ACVR2 in 25 of 28 MSI colorectal and pancreatic cancers. In addition, a mutation in the ACVR2 gene combined with loss of the wild-type allele was found in a non-MSI pancreatic cancer. This evidence is compatible with a high degree of selection for inactivation of the ACVR2 gene in tumorigenesis, supporting ACVR2 as a candidate tumor suppressor gene in gastrointestinal cancers.
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evidence of selection for clones having genetic inactivation of the activin a type ii receptor acvr2 gene in gastrointestinal cancers
Cancer Research, 2003Co-Authors: Paula M Hempen, Ravi K Bansal, Kathleen M Murphy, Robert H Whitehead, Anirban Maitra, Christine A Iacobuziodonahue, Bert Vogelstein, Lin Zhang, Sanford D MarkowitzAbstract:The activin signaling pathway parallels the transforming growth factor (TGF)-beta pathway. Both use extracellular ligands and cell surface receptors that are structurally and functionally related, as well as the same intracellular mediators (SMADs 2-4) to transmit these signals. Members of both pathways have been characterized previously as tumor suppressor genes on the demonstration of inactivating mutations in human neoplasms, e.g., genetic inactivation of the activin type I receptor was reported recently in pancreatic cancer. Here, we present evidence of selection for mutations of the activin A type II receptor (ACVR2) gene during human gastrointestinal carcinogenesis. Two 8-bp polyadenine tracts of the ACVR2 gene are targets for inactivating frameshift mutations in gastrointestinal neoplasms having microsatellite instability (MSI). These mutations are similar to those of the 10-bp polyadenine tract within the TGF-beta type II receptor (TGFBR2), a well-characterized target of frameshift mutations in the same neoplasms. We identified biallelic mutations of ACVR2 in 25 of 28 MSI colorectal and pancreatic cancers. In addition, a mutation in the ACVR2 gene combined with loss of the wild-type allele was found in a non-MSI pancreatic cancer. This evidence is compatible with a high degree of selection for inactivation of the ACVR2 gene in tumorigenesis, supporting ACVR2 as a candidate tumor suppressor gene in gastrointestinal cancers.
Guiying Wang - One of the best experts on this subject based on the ideXlab platform.
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the mir 590 ACVR2A terf1 axis regulates telomere elongation and pluripotency of mouse ipscs
Stem cell reports, 2018Co-Authors: Qidong Liu, Guiying Wang, Yao Lyu, Mingliang Bai, Zeyidan Jiapaer, Wenwen Jia, Tong Han, Rong Weng, Yiwei Yang, Jiuhong KangAbstract:During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (ACVR2A) is the downstream target and mediates the function of miR-590. Downregulation of ACVR2A promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shACVR2A-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs.
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The miR-590/ACVR2A/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs
'Elsevier BV', 2018Co-Authors: Qidong Liu, Guiying Wang, Yao Lyu, Mingliang Bai, Zeyidan Jiapaer, Wenwen Jia, Tong Han, Rong Weng, Yiwei YangAbstract:Summary: During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (ACVR2A) is the downstream target and mediates the function of miR-590. Downregulation of ACVR2A promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shACVR2A-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. : In this article, Kang and colleagues elucidate the critical function and regulatory mechanism of the miR-590/ACVR2A/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. These findings not only determined the miR-590/ACVR2A/Terf1 axis on regulating both telomere elongation and pluripotency but also revealed an underlying mechanism pushing forward the maturation of the pre-iPSCs. Keywords: miR-590, ACVR2A, Terf1, iPSCs, pluripotency, telomer
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a mir 590 ACVR2A rad51b axis regulates dna damage repair during mesc proliferation
Stem cell reports, 2014Co-Authors: Qidong Liu, Guiying Wang, Yafang Chen, Dandan Yang, Jiuhong KangAbstract:Embryonic stem cells (ESCs) enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF), which maintains the self-renewal capability of mouse ESCs (mESCs), significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB) and double-strand break (DSB) damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (ACVR2A) to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR) gene, Rad51b, as a downstream molecule of the miR-590/ACVR2A pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/ACVR2A/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal.