RNA-seq of lungs from SCID mice pre-treated with EVs from Tsc1-null or wild-type E15.5 neural progenitors prior to ELT3 cell injection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1316871 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pulmonary lymphangioleiomyomatosis (LAM) is a rare metastatic sarcoma characterized by the abnormal proliferation and dissemination of TSC1/TSC2-null smooth muscle-like cells. While extracellular vesicles (EVs) are known to regulate cancer metastasis, their roles in LAM have not been fully elucidated. Here, we identify distinct LAM-EV subtypes derived from primary tumor or metastasizing LAM cells that promote metastasis via ITGα6/β1–c-Src–FAK signaling. These EVs enhance LAM cell migration, invasion, and stemness by either shuttling ATP synthesis to cell pseudopodia or activating integrin adhesion complexes. In vivo, CD9⁺CD63⁺CD81⁺ EVs isolated from Tsc1-null or wild-type E15.5 mouse embryonic neural progenitors were labeled and injected intravenously into SCID mice, followed 48 hours later by intravenous injection of 0.5×10⁶ ELT3 cells, a well-characterized LAM model. Lungs were harvested 72 hours post-injection for RNA-seq analyses. Lungs from Tsc1-null EV-treated mice showed increased metastatic burden (rat DNA content) and differential expression of 815 genes (522 upregulated, 293 downregulated) compared to wild-type EV-injected mice. Reactome analysis revealed enrichment in extracellular matrix remodeling, collagen biosynthesis, and the assembly of multimeric structures. These findings establish EVs as key mediators of LAM metastasis and identify them as potential therapeutic targets.
2025-09-05 | GSE307366 | GEO
Project description:Memory CD8+ T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, or the effector pathways regulated by mTOR, in this process. We describe here that tuberous sclerosis 1 (Tsc1), a regulator of mTOR signaling, plays a crucial role in promoting the differentiation and function of memory CD8+ T cells in response to Listeria monocytogenes infection. Mice with specific deletion of Tsc1 in antigen-experienced CD8+ T cells evoked normal effector responses, but were markedly impaired in the generation of memory T cells and their recall responses to antigen re-exposure in a cell-intrinsic manner. Tsc1 deficiency suppressed the generation of memory-precursor effector cells (MPECs) while promoting short-lived effector cell (SLEC) differentiation. Functional genomic analysis indicated that Tsc1 coordinated gene expression programs underlying immune function, transcriptional regulation and cell metabolism. Furthermore, Tsc1 deletion led to excessive mTORC1 activity and dysregulated cellular metabolism including glycolytic and oxidative metabolism. These findings establish a Tsc1-mediated checkpoint in linking immune signaling and cell metabolism to orchestrate memory CD8+ T cell development and function. We used microarrays to explore the gene expression profiles differentially expressed in OVA-specific CD8+ T-cells from wild-type (WT; Tsc1-fl/fl and cre-negative) and Tsc1-/- (Tsc1-fl/fl and Granzyme B-cre-positive) mice
2014-09-20 | E-GEOD-61591 | biostudies-arrayexpress
Project description:We report here the adipocyte-specific ablation of Tsc1 and its affects on lactation and mammary gland function. In this dataset, mammary glands from wild-type and adipocyte Tsc1 knockout mice were isolated during lactation and analysed by RNAseq. Deletion of Tsc1 is predicted to activate mTORC1 in both peripheral and mammary adipocytes. This study demonstrates that deletion of Tsc1 in adipocytes changes mammary gland histology, and function resulting in changes to breastmilk composition.
2021-05-28 | GSE175620 | GEO
Project description: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. Naïve CD4 and CD8 T cells from wild-type and Tsc1-deficient mice (in triplicates each group) were stimulated with or without TCR signaling. RNA was analyzed by microarrays. WT/KO for 0 and 4 hr for CD4 (triplicates), and WT/KO for 0 hr for CD8 (duplicates).
2011-07-11 | E-GEOD-29797 | biostudies-arrayexpress
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
Project description:Metabolic fitness of T cells is crucial for immune responses against infections and tumorigenesis. Both the T cell receptor (TCR) signal and environmental cues contribute to the induction of T cell metabolic reprogramming, but the underlying mechanism is incompletely understood. Here we identified the E3 ubiquitin ligase Peli1 as an important regulator of T cell metabolism and antitumor immunity. Peli1 ablation profoundly promotes tumor rejection, associated with increased tumor-infiltrating CD4 and CD8 T cells. The Peli1-deficient T cells display markedly stronger metabolic activities, particularly glycolysis, than wildtype T cells. Peli1 controls the activation of a metabolic kinase, mTORC1, stimulated by both the TCR signal and growth factors, and this function of Peli1 is mediated through regulation of the mTORC1-inhibitory proteins, TSC1 and TSC2. Peli1 mediates non-degradative ubiquitination of TSC1, thereby promoting TSC1-TSC2 dimerization and TSC2 stabilization. These results establish Peli1 as an important regulator of T cell metabolism and antitumor immunity and suggest a novel mechanism that controls mTORC1 activation.
2020-11-23 | PXD020734 | Pride
Project description:Identification of transcriptional profile of several genes involved in diabetes in islet-derived extracellular vesicles (Evs). Recently, EVs are identified as a new mechanism in cell-to-cell communication by transfer of protein and genic information (mRNA, microRNA). Their role is under investigation in immunology, stem cell and cancer, but not in islets and diabetes. The aim of this experiment is to identify mRNA transcripts (in particular, mRNA transcripts involved in diabetes pathophysiology) present in islet Evs.
2012-08-02 | E-MEXP-3695 | biostudies-arrayexpress
Project description:We characterized the transcriptomic effects of chronic mTOR activation in aortic SMCs using a conditional genetic model to delete Tsc1 under control of a smooth muscle-specific Myh11 promoter
2019-08-02 | GSE135177 | GEO
Project description:We report RNA-seq results from liver tissues of control mice, liver-specific Tsc1 knockout mice, liver-specific Depdc5 knockout mice and liver-specific Tsc1/Depdc5 double knockout mice.
2020-04-14 | GSE136684 | GEO