Desert Hedgehog Downregulation Mediates Proliferative Inhibition by γ-Glutamylcyclotransferase Knockdown in Murine Glioblastoma Stem Cells
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PROVIDER: PRJNA1106010 | ENA |
REPOSITORIES: ENA
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Project description:Glioblastoma is the most frequent type of adult-onset malignant brain tumors and has a very poor prognosis. A cell population called glioblastoma stem cells has been shown to be one of the mechanisms by which glioblastoma acquires therapy resistance. Therefore, there is a need to establish novel therapeutic strategies useful for inhibiting the cell population. γ-glutamylcyclotransferase (GGCT) is an enzyme involved in the synthesis and metabolism of glutathione, which is highly expressed in a wide range of cancer types including glioblastoma, and inhibition of its expression has been reported to have antitumor effects on various cancer types. In this study, we searched for pathways affected by the growth-promoting effect of GGCT overexpression in mouse embryonic fibroblasts NIH3T3 by comprehensive gene expression analysis and found the hedgehog pathway. Knockdown of GGCT inhibited proliferation of glioblastoma stem cells derived from a mouse glioblastoma model and caused decreased expression of desert hedgehog (Dhh), a representative ligand of the pathway, and the downstream target Gli1. To analyze the contribution of reduced Dhh, we activated the hedgehog pathway by forced expression of Dhh. We found that Dhh overexpression significantly restored the growth suppressive effect of GGCT knockdown. The results of this study indicate that high GGCT expression is important for Dhh expression and activation of the hedgehog pathway, which is required to maintain glioblastoma stem cell proliferation. Therefore, inhibition of GGCT function may be useful in suppressing stemness of glioblastoma stem cells accompanied with activation of the hedgehog pathway.
2024-05-20 | GSE266154 | GEO
Project description:Regulation of erythropoiesis in the spleen by Desert Hedgehog (Dhh)
| PRJNA843316 | ENA
Project description:Postnatal tissue quiescence is generally thought to be a default state in the absence of a proliferative stimulus such as injury. We now demonstrate that in the lung, quiescence in the adult is an actively maintained state and is regulated by paracrine hedgehog signaling. Epithelial-specific deletion of Sonic Hedgehog during normal homeostasis results in a proliferative expansion of the adjacent lung mesenchyme. Injury to the lung epithelium results in decreased hedgehog activation, accompanied by proliferative expansion of the adjacent mesenchyme. Moreover, reconstitution of Hedgehog signaling during epithelial injury attenuated the proliferative expansion of the adjacent mesenchyme. Hedgehog signaling maintains lung quiescence by attenuating PDGF signaling through blocking post-translational processing of PDGF receptor α/β into the mature isoforms. These results indicate that in postnatal tissues, epithelial cells can actively maintain mesenchymal quiescence via paracrine hedgehog activation, and that imbalances in this pathway could lead to aberrant mesenchymal expansion and postnatal disease. Fibroblasts were isolated from mouse lungs and grown in culture in triplicate wells. Samples were treated with vehicle or purmorphamine 5um for 24 hours and RNA was isolated for microarray.
2016-07-03 | E-GEOD-61026 | biostudies-arrayexpress
Project description:Physiologically, trophoblast progenitor cells differentiate into placental villous cytotrophoblast cells (CTBs). CTBs either differentiate into invasive lineage to yields extravillous cytotrophoblast cells (EVTs), or undergo cell fusion lineage to yields syncytiotrophoblast cells (STBs)，Sonic hedgehog (Shh) together with indian hedgehog (Ihh) and desert hedgehog (Dhh) consist of ligand of hedgehog signaling pathway, which plays pivotal roles in regulating cell proliferation, cell differentiation, organogenesis and development, even involving in tumorigenesis and progression. previous study had summarized and indicatedthat hedgehog proteins played important roles in regulating hematopoiesis, vasculogenesis and angiogenesis during embryogenesis and development. Herein, we investigate the effect of the Sonic Hedgehog morphogen inhibitor Cyclopamine on JAR cells
2019-12-31 | GSE130367 | GEO
Project description:Postnatal tissue quiescence is generally thought to be a default state in the absence of a proliferative stimulus such as injury. We now demonstrate that in the lung, quiescence in the adult is an actively maintained state and is regulated by paracrine hedgehog signaling. Epithelial-specific deletion of Sonic Hedgehog during normal homeostasis results in a proliferative expansion of the adjacent lung mesenchyme. Injury to the lung epithelium results in decreased hedgehog activation, accompanied by proliferative expansion of the adjacent mesenchyme. Moreover, reconstitution of Hedgehog signaling during epithelial injury attenuated the proliferative expansion of the adjacent mesenchyme. Hedgehog signaling maintains lung quiescence by attenuating PDGF signaling through blocking post-translational processing of PDGF receptor α/β into the mature isoforms. These results indicate that in postnatal tissues, epithelial cells can actively maintain mesenchymal quiescence via paracrine hedgehog activation, and that imbalances in this pathway could lead to aberrant mesenchymal expansion and postnatal disease.
2016-01-01 | GSE61026 | GEO
Project description:Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in the hedgehog developing gut at E13.5, Differential gene expression analysis along the hedgehog developing gut
2013-10-23 | E-GEOD-44696 | biostudies-arrayexpress
Project description:Streptomyces huasconensis strain:desert | isolate:desert Genome sequencing
| PRJNA708196 | ENA