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Chronic AMPK inactivation slows SHH medulloblastoma progression by inhibiting mTORC1 and depleting tumor stem cell populations

ABSTRACT: We report scRNA-seq data showing the effect of Prkaa1/2 deletion on medulloblastomas that form in Smo-mutant mice. We generate tumor-bearing mice by breeding hGFAP-Cre/Prkaa1fl/fl/Prk112fl/fl and Prkaa1fl/fl/Prk112fl/fl/SmoM2 mouse lines to prodce tumor-prone progeny with homozygous, conditional deletion of Prkaa1 and Prkaa2 (G-SmoAMPK mice). We compared tumors from G-Smo mice withintact Prkaa1 and Prkaa2 to tumors from G-SmoAMPK mice, using Drop-seq-based scRNA-seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE190297 | GEO | 2021/12/08

REPOSITORIES: GEO

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Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq-guided combination with sapanisertib

Project description:We report scRNA-seq data showing the effect of palbociclib treatment on medulloblastomas that form in Smo-mutant mice. We generate tumor-bearing mice by breeding hGFAP-Cre and SmoM2 mouse lines to prodce tumor-prone progeny heterozygous for both transgenes (G-Smo mice). We compare tumors from untreated G-Smo mice to tumors from G-Smo ice treated with nanoparticle--delievered palbociclib, using Drop-seq-based scRNA-seq.

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Gene expression profiling of constitutive activation of Smoothened in the mouse uterus

Project description:In order to gain a better understanding of Ihh action during embryo implantation, we constitutively activated Smo in the murine uterus using the PRcre mouse model (PRcre/+SmoM2+; SmoM2). Female SmoM2 mice were infertile. They exhibited normal serum progesterone levels and normal ovulation, but ova failed to be fertilized in vivo and the uterus failed to undergo the artificially induced decidual response. SmoM2 mice exhibited uterine hypertrophy. The endometrium had a reduced number of uterine glands and the endometrial stroma lost its normal morphologic characteristics. Microarray analysis of 3 month old SmoM2 uteri demonstrated a chondrocytic signature and confirmed that constitutive activation of SmoM2 increased extracellular matrix production. Thus, constitutive activation of Smo in the mouse uterus alters the extracellular matrix which interferes with early pregnancy. Keywords: two group comparison We constitutively activated Hh signaling in the uterus by the expression of a mutant SmoM2 allele. We crossed these mice to the PRcre mouse model to constitutively activate Smo in the murine uterus (PRcre/+SmoM2+; SmoM2). High density DNA microarray analysis was performed on 3 month old control and SmoM2 uteri.

2010-04-13 | E-GEOD-17263 | biostudies-arrayexpress

Gene expression profiling of constitutive activation of Smoothened in the mouse uterus

2010-04-13 | GSE17263 | GEO

An essential role for the Gai2 protein in Smoothened-stimulated mammary epithelial cell proliferation

Project description:Hedgehog (Hh) signaling is critical for organogenesis, tissue homeostasis, and stem cell maintenance. Smoothened (SMO), the primary effector of Hh signaling, is expressed ectopically in human breast cancer, as well as in other cancers. Constitutive activation of SMO in mouse mammary glands leads to paracrine stimulation of proliferation, as well as hyperplasia. In canonical signaling, SMO functions via GLI transcription factor activation. However, recent data from Drosophila and mammalian cell lines indicate that SMO can function non-canonically as a G-protein coupled receptor (GPCR) by coupling to heterotrimeric G proteins, particularly those in the pertussis toxin (PTX)-sensitive G-alpha-i (Gai) class. Whether SMO functions as a GPCR in mammalian tissues in vivo is not known. Using genetically modified mouse models, we demonstrate here that SMO-induced stimulation of proliferation is PTX sensitive, and requires Gai2, but not Gai1 or Gai3. Our findings provide evidence for a non-canonical GPCR function of activated SMO in vivo, a finding that may have clinical significance given that most SMO-targeted agents were selected based largely on their ability to block canonical GLI-mediated transcription. Primary mammary epithelial cell RNA was deep-sequenced from mT-mG/SmoM2;MMTV-Cre (EGFP), mT-mG/SmoM2;MMTV-Cre (tdTomato), and mT-mG/SmoM2;+ cells to examine the effects of SmoM2 overexpression in the mammary gland.

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2023-06-12 | GSE221389 | GEO

Gene expression in mice with conditional over-activation of hedgehog signaling in the ovary

2012-03-14 | GSE35123 | GEO

Mechanosensing brain tumor cells construct blood-tumor barrier to mask chemosensitivity

Project description:This dataset includes the raw single-cell RNAseq data from Math1-Cre;SmoM2 and Math1-Cre;SmoM2;Piezo2 fl/fl mouse medulloblastoma model. In this project, we focused on transcriptomic alteration caused by Piezo2 knockout in Sox2 positive MB initiation cells.

2022-09-22 | GSE197402 | GEO

E-MTAB-5077

Project description:RNA sequencing of microglia sorted form tamoxifen treated Sall1CreER/fl and control Sall1fl/fl mice

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2019-07-09 | GSE103235 | GEO

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