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Tsc2 coordinates differentiation

ABSTRACT: Multipotent neural stem cells (NSCs) that reside within the ventricular-subventricular zone (V-SVZ) of the brain generate a variety of cell types. Here we provide transcriptomes of NSCs that have lost Tsc2 as occurs in the neurodevelopmental disorder Tuberous Sclerosis Complex (TSC).

ORGANISM(S): Mus musculus

PROVIDER: GSE229276 | GEO | 2023/10/16

REPOSITORIES: GEO

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Tsc2 coordinates differentiation [bulkRNA-seq]

Project description:Multipotent neural stem cells (NSCs) that reside within the ventricular-subventricular zone (V-SVZ) of the brain generate a variety of cell types. Here we provide transcriptomes of NSCs that have lost Tsc2 as occurs in the neurodevelopmental disorder Tuberous Sclerosis Complex (TSC).

2023-10-16 | GSE229552 | GEO

Tsc2 coordinates differentiation [scRNA-seq]

Project description:Multipotent neural stem cells (NSCs) that reside within the ventricular-subventricular zone (V-SVZ) of the brain generate a variety of cell types. Here we provide transcriptomes of cells that have lost Tsc2 as occurs in the neurodevelopmental disorder Tuberous Sclerosis Complex (TSC).

2023-10-16 | GSE229549 | GEO

Tsc2 shapes olfactory bulb granule cell molecular and morphological characteristics

Project description:Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations that inactivate TSC1 or TSC2. Hamartin and tuberin are encoded by TSC1 and TSC2 which form a GTPase activating protein heteromer that inhibits the Rheb GTPase from activating a growth promoting protein kinase called mammalian target of rapamycin (mTOR). Growths and lesions occur in the ventricular-subventricular zone (V-SVZ), cortex, olfactory tract, and olfactory bulbs (OB) in TSC. Here, nestin-CRE-ERT2 mice were injected with tamoxifen at postnatal days 2 and 3 and brains harvested at postnatal day 60. OBs were subsequently subjected to RNA sequencing.

2022-06-19 | GSE206287 | GEO

Ribosome profiling and RNA-seq of Tsc2+/- hippocampal slices

Project description:Tuberous sclerosis (TSC) is caused by loss of function in Tsc2 and haploinsufficiency of the protein product tuberin.

2020-10-05 | GSE144539 | GEO

Drosophila S2R+ / TSC1 / TSC2 mutant phosphoproteomics

Project description:The tuberous sclerosis complex (TSC) family of tumor suppressors, TSC1 and TSC2, function together in an evolutionarily conserved protein complex that is a point of convergence for major cell signaling pathways that regulate mTOR complex 1 (mTORC1). Mutation or aberrant inhibition of the TSC complex is common in various human tumor syndromes and cancers. The discovery of novel therapeutic strategies to selectively target cells with functional loss of this complex is therefore of substantial clinical relevance to TSC and sporadic cancers. We developed a CRISPR-based method to generate homogenous mutant Drosophila cell lines. By combining TSC1 and TSC2 mutant cell lines with RNAi screens against all kinases and phosphatases, we identified synthetic interactions with TSC1 and TSC2. Knockdown of three candidate genes (mRNA-cap, Pitslre and CycT; orthologs of RNGTT, CDK11 and CCNT1 in humans) reduced the population growth rate of both Drosophila TSC1 and TSC2 mutant cells but not that of wild-type cells. Moreover, knockdown of all three genes displayed similar selective effects in mammalian TSC2-deficient cell lines, including human tumor-derived cells, illustrating the power of this cross species screening strategy to identify potential drug targets.

2018-10-24 | PXD002670 | Pride

Transcriptome analysis of TSC1 and TSC2 using Nanopore long-read sequencer

Project description:Tuberous sclerosis complex (TSC) is a relatively common autosomal dominant disorder characterized by multiple dysplastic organ lesions and neuropsychiatric symptoms, caused by loss-of-function mutation of either TSC1 or TSC2. Target-capture full-length double-stranded cDNA sequencing using long-read sequencer Nanopore (Nanopore Long-read Target Sequencing) revealed that the various kinds of the TSC1 and TSC2 full-length transcripts and the novel intron retention transcripts of TSC2 in TSC patient. Our results indicate that the Nanopore Long-read Target Sequencing is useful for the detection of mutations and confers information on the full-length alternative splicing transcripts for the genetic diagnosis.

2023-09-04 | GSE241410 | GEO

Identity and Nature of Neural Stem Cells in the Adult Human Subventricular Zone

Project description:The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early-lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

2023-12-27 | GSE248995 | GEO

A defect in protein farnesylation suppresses a loss of fission yeast tsc2

Project description:Human Tsc1 and Tsc2 genes predispose to Tuberous Sclerosis Complex (TSC), a disorder characterized by the widespread of benign tumors. Tsc1 and Tsc2 proteins form a complex and serve as a GAP (GTP activating protein) for Rheb, a GTPase regulating a downstream kinase, mTor. The fission yeast genome contains tsc1+ and tsc2+, homologs of human Tsc1and Tsc2, respectively. In this study we analyzed gene expression profile in a genome-wide scale and found that deletion of either tsc1+ or tsc2+ affects gene induction upon nitrogen starvation. Three hours after nitrogen depletion genes encoding permeases and genes required for meiosis are less induced. Under the same condition, retrotransposons, G1-cyclin (pas1+) and a gene normally repressed by glucose (inv1+) are more induced. We also demonstrate that a mutation (cpp1-1) in a gene encoding aβ-subunit of a farnesyl transferase can suppress most of the phenotypes associated with deletion of tsc1+ or tsc2+. When a mutant of rhb1+ (homolog of human Rheb), which bypasses the requirement of protein farnesylation, was expressed, the cpp1-1 mutation could no longer suppress, indicating that deficient farnesylation of Rhb1 contributes to the suppression. Based on these results, we discuss the TSC-pathology and possible improvement in chemotherapy for TSC. Keywords: Keywards: Nitrogen starvation, Dtsc1. Dtsc2

2006-06-13 | GSE4449 | GEO

Dnmt3a-dependent non-promoter DNA methylation facilitates transcription of neurogenic genes

Project description:This SuperSeries is composed of the following subset Series: GSE22473: Murine postnatal subventricular zone (SVZ) neural stem cells (NSCs): Wild-type (WT) vs. Dnmt3a-null (KO) GSE22474: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [Agilent] GSE22475: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [NimbleGen] Refer to individual Series

2010-06-24 | E-GEOD-22476 | biostudies-arrayexpress

Olig2 Defines a Unique Subset of Neural Stem Cells That Produce Specific Olfactory Bulb Interneuron Subtypes in the Subventricular Zone of Postnatal and Adult Mice

Project description:Distinct neural stem cells reside in different regions of the subventricular zone and generate multiple olfactory bulb interneuron subtypes in the adult mouse brain. This study shows that the basic helix-loop-helix type transcription factor Olig2 defines a ventrally enriched subset of NSCs in the early postnatal and adult SVZ and plays an important role in the subtype specification of olfactory bulb interneurons produced by adult NSCs.

2022-02-18 | GSE174392 | GEO

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