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Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (EdU-Seq)

ABSTRACT: Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (EdU-Seq)

PROVIDER: PRJNA614502 | ENA |

REPOSITORIES: ENA

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Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma

Project description:Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma

| PRJNA614497 | ENA

Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (RNA-Seq)

Project description:Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (RNA-Seq)

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Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (EdU-Seq)

Project description:Cancer is a multi-stage disease caused by sequential mutations; however, the molecular mechanism generating cancer-initiating mutations for many cancers is not well understood. Using the developing cerebellum as model system, here we delineate a molecular mechanism for tumor initiation in medulloblastoma (MB), the most frequent malignant pediatric brain tumor. Activation of the Sonic hedgehog (SHH) pathway is frequent in MB, with mutations in the tumor suppressor PTCH1 (a negative regulator of SHH signaling) being the most common initiating event for SHH-MB. However, how SHH as a developmental mitogen promotes early carcinogenesis in the cells of origin, granule cerebellar progenitors (GCPs), remains to be determined. Here we report that physiological exposure of GCPs to Shh causes a distinct form of DNA replication stress, altering DNA replication dynamics to increase both origin firing and fork velocity. Shh promotes DNA helicase loading and activation in GCPs, with increased levels of Cdc7-dependent replication origin firing. S-phase duration is reduced and hyper-recombination consequently occurs. Such elevated recombination causes copy-number neutral LOH, an event seen frequently at the PTCH1/ptch1 locus. Moreover, Cdc7 inhibition to attenuate origin firing in a MB mouse model is sufficient to reduce somatic recombination and preneoplastic tumor formation. We therefore establish that tissue-specific replication stress induced by Shh acts to promote LOH, which in tumor-prone Ptch1+/- GCPs can result in loss of this tumor suppressor, as an early cancer initiating event.

2020-07-20 | GSE147409 | GEO

Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma (RNA-Seq)

2020-07-20 | GSE147410 | GEO

Sonic Hedgehog subgroup medulloblastomas

Project description:Sonic Hedgehog subgroup medulloblastomas

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Sonic Hedgehog inhibitor cyclopamine effect on JAR cells

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

Sonic hedgehog Activation Restores Interneurons and Cognitive Function in Newborns with Intraventricular Hemorrhage

Project description:We hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Since Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signaling might restore neurogenesis, cortical interneuron population, and neurobehavioral function in premature newborns with IVH.

2022-08-06 | GSE210477 | GEO

Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-07-20 | GSE147411 | GEO

Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model

Project description:The causative role of activated Hedgehog signaling in liver fibrosis was investigated in vivo. Using hydrodynamics-based transfection, a transgenic mouse model has been developed that expresses Sonic Hedgehog (SHH), a ligand for Hedgehog signaling, in the liver. Levels of hepatic fibrosis and fibrosis-related gene expression were assessed in the model.

2015-10-30 | E-GEOD-72758 | biostudies-arrayexpress

Transcriptional responses to Sonic Hedgehog pathway stimulation in in vitro derived neural progenitors

Project description:The objective of this study was to identify genes regulated by Sonic Hedgehog pathway stimulation in neural progenitors.

2012-12-15 | GSE42565 | GEO