GEO DataSets

(Submitter supplied) Rationale: Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of lymphangioleiomyomatosis (LAM). Objectives: To investigate how TSC1 or TSC2 deficiency alters MMP expression and regulation. Methods: We studied immortalized cells that lack TSC2 derived from an angiomyolipoma (AML) of a LAM patient, and a TSC2 add back derivative; and murine embryonic fibroblast cells that lack Tsc1 or Tsc2 and respective controls. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL2895

9 Samples

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(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL17021

12 Samples

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(Submitter supplied) Pulmonary Lymphangioleiomyomatosis (LAM), a rare lung disease that affects predominantly women, is characterized by proliferation of smooth muscle-like cells in the lungs, destruction of lung tissue, upregulation of VEGF-D, and growth of lymphatic vessels inducing a loss of pulmonary function. TSC2 gene mutations that render TSC2 inactive are a common finding associated with LAM. To better understand the function of the TSC2 gene, we sought to characterize differences in the transcriptome of cells where TSC2 is inactivated. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: TXT

(Submitter supplied) Pulmonary Lymphangioleiomyomatosis (LAM), a rare lung disease that affects predominantly women, is characterized by proliferation of smooth muscle-like cells in the lungs, destruction of lung tissue, upregulation of VEGF-D, and growth of lymphatic vessels inducing a loss of pulmonary function. TSC2 gene mutations that render TSC2 inactive are a common finding associated with LAM. To better understand the function of the TSC2 gene in LAM , we sought to characterize differences in the transcriptome of cells where TSC2 is inactivated. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

6 Samples

Download data: TXT

(Submitter supplied) To uncover genes regulated by mTORC1 and estradiol in uterine Tsc2-null LAM like cells, we performed RNAseq on uteri from 12-week old wild-type (WT) and uterine-specific Tsc2-null (KO) mice that were either untreated (intact), oopherectomized (ovx) or oopherectomized + treated with 17β-estradiol pellets (E2) for 8 weeks. We identified genes that were both estradiol- and TSC2-mediated.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

18 Samples

Download data: TXT

(Submitter supplied) Tuberous sclerosis complex (TSC) is an inherited multi-system disorder caused by mutations in the TSC1 or TSC2 gene. TSC patients are often diagnosed with a range of neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD), intellectual disability (ID), anxiety and mood disorders. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) kinase signaling. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

24 Samples

Download data: TXT

(Submitter supplied) Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic link, but no single well-established cause. This suggests that perturbed regulatory network may better explain its heterogeneity of phenotypes and multiple gene associations. Consistently, our previous study provided evidence of abnormal alternative polyadenylation in transcripts from distinct brain regions suggesting a potential imbalance in the protein synthesis in the postsynaptic density. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

20 Samples

Download data: TXT

(Submitter supplied) In order to identify the genes regulated by TSC2, gene expression profiling of two clones stably overexpressing TSC2 was performed.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

4 Samples

Download data: TXT

(Submitter supplied) Syk inhibitor demonstrates antiproliferative effect on Tsc2-deficient cells and LAM lung nodules similar to rapamycin. A feedback loop between Syk inhibition and mTORC1 inhibition pathways is also present in these Tsc2-deficient cells. We used microarrays to discern the potential difference in Syk inhibition and mTORC1-inhibition pathways. The goal was to investigate regulatory pathways or targets of Syk inhibition to induce cytocidal response in Tsc2-deficient cells, independent of its crosstalk with mTORC1 signaling.

Organism:

Rattus norvegicus

Type:

Expression profiling by array

Platform:

GPL17799

12 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL17021 GPL16791

34 Samples

Download data: CSV, H5

(Submitter supplied) Tumor suppressor Tuberous sclerosis complex 2 (TSC2) is a key negative regulator of mammalian target of rapamycin (mTOR), a central controller of cell growth and metabolism in health and disease. Loss of TSC2 induces the constitutive activation of mTORC1 in rare lung disease pulmonary Lymphangioleiomyomatosis (LAM), which affects only women of childbearing age and characterized by lung destruction and progressive loss of pulmonary function. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

30 Samples

Download data: CSV

(Submitter supplied) Investigate detailed cellular composition of the LAM lung compared to the age and sex matched healthy control, in order to isolate LAM-lung-specific cellular states or subtypes.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

4 Samples

Download data: H5

(Submitter supplied) Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL96

25 Samples

Download data: CEL

(Submitter supplied) Tuberous Sclerosis Complex (TSC) is caused by germline TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and tumors in multiple organs including the brain, heart, lung (lymphangioleiomyomatosis), and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in models of TSC. To determine the impact of TFEB in vivo, we generated two novel mouse models of TSC, resulting in premature death, in which kidney pathology was the primary phenotype. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

42 Samples

Download data: TXT

(Submitter supplied) Tuberous sclerosis complex (TSC) is a multisystem tumor-forming disorder caused by loss of TSC1 or TSC2. Renal manifestations predominately include cysts and angiomyolipomas. Despite a well-described monogenic etiology, the cellular pathogenesis has remained elusive. Here, we report a novel genetically-engineered human renal organoid model which recapitulates pleiotropic features of TSC kidney disease in vitro and upon orthotopic xenotransplantation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

3 Samples

Download data: CSV, RDS

(Submitter supplied) Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease caused by tuberous sclerosis complex 1/2 (TSC1/2) gene mutations resulting in activation of the mechanistic target of rapamycin complex 1 (mTORC1). A subset of LAM patients develops pulmonary vascular remodeling and pulmonary hypertension. To model LAM disease, we utilized an mTORC1 gain-of-function mouse model with a Tsc2 knock-out (Tsc2KO) specific to lung mesenchyme (Tbx4LME-CreTsc2fl/fl), similar to the mesenchyme specific genetic alterations seen in human disease. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

2 Samples

Download data: MTX, TSV

(Submitter supplied) We report results of RNA sequencing analysis of serum starved UMB1949 renal angiomyolipoma (AML) cells comparatively treated for 24hrs at 37C and 5% CO2 with rapamycin (0.05uM and 1uM) and tyrosine kinase inhibitor (TKI) imatinib (1uM and 10uM). Experiments were done in triplicates per drug concentration. This study was performed to investigate the biological mechanisms underlying superior cytocidal capabilities of the TKI over FDA-approved rapamycin by inhibiting receptor tyrosine kinases on mesenchymal tumorigenic cells in Tuberous Sclerosis and Lymphangioleiomyomatosis (LAM) diseases. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

15 Samples

Download data: H5, TSV, TXT

(Submitter supplied) We report results of RNA sequencing analysis of serum starved pulmonary LAM tumor cells comparatively treated for 24hrs at 37C and 5% CO2 with rapamycin (0.05uM and 1uM) and tyrosine kinase inhibitor (TKI) imatinib (1uM, 5uM, and 10uM). Experiments were done in duplicates per drug concentration. This study was performed to investigate the biological mechanisms underlying superior cytocidal capabilities of the TKI over FDA-approved rapamycin by inhibiting receptor tyrosine kinases on mesenchymal tumorigenic cells in Tuberous Sclerosis and Lymphangioleiomyomatosis (LAM) diseases. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: TAR, TXT

(Submitter supplied) The mechanisms that regulate T cell quiescence are poorly understood. We report that tuberous sclerosis complex 1 (Tsc1) establishes a quiescent program in naïve T cells by controlling cell size, cell cycle entry, and responses to T cell receptor stimulation. Loss of quiescence predisposed Tsc1-deficient T cells to apoptosis that depleted conventional T cells and invariant natural killer T cells. Loss of Tsc1 function dampened in vivo immune responses to bacterial infection. Tsc1-deficient T cells exhibited increased mTORC1 but diminished mTORC2 activities, with mTORC1 activation essential for the disruption of immune homeostasis. Therefore, Tsc1-dependent control of mTOR is crucial in establishing naïve T cell quiescence to facilitate adaptive immune function.

Organism:

Mus musculus

Type:

Expression profiling by array

Datasets:

GDS4434 GDS4572

Platform:

GPL11180

16 Samples

Download data: CEL

Analysis of naïve CD4 and CD8 T cells deficient for Tuberous sclerosis complex 1 (Tsc1). Tsc1 tumor suppressor is an mTOR signaling modulator involved in naive T cell quiescence and immune homeostasis regulation. Results identify a Tsc1-dependent gene signature in naive T cells.

Organism:

Mus musculus

Type:

Expression profiling by array, transformed count, 2 cell type, 2 genotype/variation sets

Platform:

GPL11180

Series:

GSE29797

10 Samples

Download data: CEL