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Profiling gene expression in 32Dcl3 cells following Xbp1 retrovirus vector transfection

ABSTRACT: The significant changes of hematopoietic cells induced by Xbp1S expression indicate that there is global alteration in gene expression. UPR induces transcription of Xbp1, and phosphorylation of the ER transmembrane kinase IRE1 initiates UPR-mediated mRNA splicing of Xbp1, resulting in the production of Xbp1S, an active form of a basic leucine zipper transcription factor. In the present study, Xbp1S retrovirus vector infected 32cl3 cells show cell cycle arrest and myeloid differentiation. Xbp1S may modulate important genes of differentiation and the cell cycle.

ORGANISM(S): Mus musculus

PROVIDER: GSE17023 | GEO | 2010/10/01

SECONDARY ACCESSION(S): PRJNA117803

REPOSITORIES: GEO

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Profiling gene expression in 32Dcl3 cells following Xbp1 retrovirus vector transfection

Project description:The significant changes of hematopoietic cells induced by Xbp1S expression indicate that there is global alteration in gene expression. UPR induces transcription of Xbp1, and phosphorylation of the ER transmembrane kinase IRE1 initiates UPR-mediated mRNA splicing of Xbp1, resulting in the production of Xbp1S, an active form of a basic leucine zipper transcription factor. In the present study, Xbp1S retrovirus vector infected 32cl3 cells show cell cycle arrest and myeloid differentiation. Xbp1S may modulate important genes of differentiation and the cell cycle. RNA samples extracted from 32Dcl3 cells with pMIG (empty vector), pMY-Xbp1U (unspliced form) and pMY-Xbp1S (spliced form) retroviral vector transfected cells were subjected to expression profiling using the Affymetrix GeneChip microarray system.

2010-10-01 | E-GEOD-17023 | biostudies-arrayexpress

Bulk RNAseq of control, XBP1-deficient or XBP1/IRE1-deficient cDC1s from subcutaneous B16- melanoma bearing mice

Project description:The unfolded protein response (UPR) sensor IRE1 and its target, the transcription factor XBP1s critically regulate the function of dendritic cell (DC) subtypes. However, the contribution of the IRE1/XBP1s axis in DCs to the antitumor immunity is not entirely understood. Here, using reporter mice we found that DCs, in particular type 1 conventional DCs (cDC1s), are major targets of IRE1 RNase activity in melanoma tumors. Deletion of XBP1s in CD11c+ cells resulted in augmented tumor growth, impaired effector T cell responses and decreased accumulation of TCF-1+CD8+ T cells with a precursor exhausted profile. Transcriptomic studies revealed that XBP1 deletion in tumor cDC1s induced regulated IRE1 dependent decay (RIDD) of mRNAs, which accounted for the dysregulated T cell immunity in melanoma. Thus, a strict regulatory circuit involving IRE1 RNase and XBP1s in DCs ensures optimal antitumor T cell immunity in melanoma models.

2023-05-26 | GSE195439 | GEO

Effect of neuron-specific spliced XBP1 (XBP1s) overexpression on gene expression in the mouse brain

Project description:One major component of cellular proteome resides in the endoplasmic reticulum (ER), the key organelle for protein biogenesis in the secretory pathway. Disruption of ER proteostasis leads to ER stress, which subsequently activates multiple adaptive stress response pathways, collectedly termed as the unfolded protein response (UPR). One UPR branch is mediated by IRE1(inositol-requiring enzyme 1). Activation of the IRE1 UPR branch generates a potent transcriptional factor: spliced X-box–binding protein-1 (XBP1s). Since activation of this UPR branch has been shown to be neuroprotective in brain ischemia/stroke, it is critical to identify the XBP1s-regulated genes in neurons in vivo and thus help determine the molecular mechanisms underlying the beneficial effects exerted by this UPR branch. In this study, we performed RNA-Seq analysis on the hippocampus from XBP1s conditional transgenic mice.

2022-10-22 | GSE160263 | GEO

Genome-wide mRNA profiling identifies X-box-binding protein 1 (XBP1) as an IRE1 and PUMA repressor

Project description:Previous studies suggested that XBP1s is important in deciding cell fate during the UPR, however, the mechanistic details of how it modulates this transition are limited. To search for XBP1s transcriptional targets, we utilized an XBP1s-inducible human cell line to limit XBP1 expression in a controlled manner.

2021-10-12 | GSE160416 | GEO

Expression data from human multiple myeloma cells with or without IRE1-XBP1 silencing

Project description:We used microarrays to develop gene signatures for XBP1 and IRE1 in myeloma cells to explore the role of this UPR/differentiation pathway in proteasome inhibitor resistance.

2013-03-09 | GSE44968 | GEO

Expression data from IRE1a or XBP1 deficient mouse liver

Project description:IRE1a and XBP1 are key regulators of the unfolded protein response (UPR). XBP1 ablation causes profound hypolipidemia in mice, and triggers feedback activation of its upstream enzyme IRE1a, instigating regulated IRE1-dependent decay (RIDD), an mRNA degradation mechanism dependent on IRE1a's endoribonuclease activity. Comprehensive microarray analysis of XBP1 and/or IRE1a deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1a. To identify RIDD substrate mRNAs and direct XBP1 targets in the liver, we performed a comprehensive comparative microarray analysis of three groups of RNA samples: WT and XBP1 deficient mice, WT and IRE1a deficient mice untreated or injected with tunicamycin, and XBP1 deficient mice injected with luciferase or IRE1a siRNA.

2012-10-17 | E-GEOD-40515 | biostudies-arrayexpress

Expression data from IRE1a or XBP1 deficient mouse liver

2012-10-17 | GSE40515 | GEO

The IRE1Î±-XBP1 Pathway of the Unfolded Protein Response is Required for Adipogenesis

Project description:Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARÎ³ and C/EBPÎ±. Here we demonstrate that the IRE1Î±-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1Î± knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPÎ², a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1Î± is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1Î±-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis. The Xbp1 deficient MEFs are subjected to adipogenesis using standard drug induction. The cells are collected at day 0 and day 3. Total RNA are extracted from the cells and used for one channel microarray analysis. Expression levels on day 3 are compared to that on day 0.

2010-06-19 | E-GEOD-15771 | biostudies-arrayexpress

Expression data from human multiple myeloma cells with or without IRE1-XBP1 silencing

Project description:We used microarrays to develop gene signatures for XBP1 and IRE1 in myeloma cells to explore the role of this UPR/differentiation pathway in proteasome inhibitor resistance. RPMI-8226 and JJN3 human myeloma cells were infected with lentivirus expressing non-targeted (NT) shRNA, shIRE1 or shXBP1 and processed for RNA extraction and hybridization on Affymetrix microarrays. Cells without lentiviral infection were processed as controls for gene expression changes related to the cellular response to lentivirus.

2013-03-09 | E-GEOD-44968 | biostudies-arrayexpress

The IRE1α-XBP1 Pathway of the Unfolded Protein Response is Required for Adipogenesis

Project description:Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARγ and C/EBPα. Here we demonstrate that the IRE1α-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1α knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPβ, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1α is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1α-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis.

2009-04-25 | GSE15771 | GEO

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