Investigating the role of USP22 in reprogramming
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA934088 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23434163_1.fastq.gz | Fastqsanger.gz | |||
| SRR23434163_2.fastq.gz | Fastqsanger.gz | |||
| SRR23434164_1.fastq.gz | Fastqsanger.gz | |||
| SRR23434164_2.fastq.gz | Fastqsanger.gz | |||
| SRR23434165_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by overexpressing OCT4, SOX2, KLF4 and MYC. Although this cell fate transition is a slow and inefficient process, inhibiting several epigenetic barriers has shown to facilitate it. A previously employed epigenetic focused CRISPR-Cas9-mediated knockout screen during reprogramming uncovered novel human somatic cell reprogramming barriers. Here, I showed that USP22, target for gRNAs that were enriched in iPSCs from the screen, is a barrier for reprogramming and its loss is compatible with iPSC generation. Overexpressing wild-type or deubiquitinase mutant (C185A) USP22 in knockout background could rescue the phenotype. Additionally, knocking out other SAGA deubiquitinase subunits, ENY2 and ATXN7L3 did not increase the reprogramming efficiency. Mechanistically, we showed that USP22 loss upregulates an important pluripotency-related transcription factor, SOX2, expression even as early as 3 days after OSKM expression. We hypothesized that USP22 downregulates pluripotency-related gene expression during reprogramming independent from its SAGA integration and deubiquitinase activity. To address this, I will repeat rescuing USP22 knockout phenotype in reprogramming by overexpressing mutant versions of USP22 including K129R (acetyl inhibited) and HHAA (deubiqutinase). Additionally, I will check the expression of pluripotency-related genes at early time points of reprogramming upon USP22 knockout by transcriptome profiling. Lastly, I will generate USP22 knockout iPSC lines to force them to differentiation to observe if they have any problem with pluripotency exit. This work will establish a mechanistic understanding for the role USP22 play on both human somatic cell reprogramming, pluripotency and differentiation.
2023-07-31 | GSE225151 | GEO
Project description:USP22 plays oncogenic role and in order to study molecular mechanism of USP22 to promote tumorigenesis, microarray analysis was performed on USP22 knockdowned cells.
2018-10-01 | GSE104929 | GEO
Project description:Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of monoubiquitination from histone H2B, thereby regulating gene transcription. However, novel roles for USP22 have recently emerged, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in a variety of tumor cell lines. Loss of USP22 expression significantly delays TNF/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNF-mediated NF-B activation or extrinsic apoptosis. Mass-spectrometric ubiquitin remnant profiling identified lysine 518 of Receptor-interacting protein kinase 3 (RIPK3) as USP22-dependent ubiquitination target during necroptosis induction. Mutation of K518 in RIPK3 reduced necroptosisassociated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of ubiquitination as crucial regulator of necroptotic cell death.
2021-05-03 | PXD020909 | Pride
Project description:RNA-seq analysis of sorted Usp22-WT and Usp22-KO tumor cells from subcutaneously implanted mouse pancreatic tumors
2019-11-08 | GSE140088 | GEO
Project description:Investigating the role of FOS/AP-1 in OnF reprogramming during tumor intiation
| PRJNA1095522 | ENA
Project description:Breast cancer (BC), the most frequent tumor entity in women globally, shows a high therapeutic response in early and non-metastatic stages. However, triple-negative BC (TNBC), enriched with cancer stem cells (CSCs), presents significant challenges due to its chemoresistant and metastatic nature. Ubiquitin Specific Proteinase 22 (USP22) has emerged as a key player in promoting CSC functions, contributing to resistance to conventional therapies, tumor relapse, metastasis, and poor survival across various cancers, including BC. The specific role of USP22 in TNBC, however, remains underexplored. In this study, we employed the MMTV-cre, Usp22fl/fl transgenic mouse model to investigate USP22's influence on stem cell-like properties in mammary tissue. High-throughput transcriptomic analyses, combined with publicly available patient data and TNBC culture models, were utilized to elucidate USP22's role in CSC characteristics of TNBC. Our findings reveal that USP22 enhances CSC properties and drug tolerance by supporting oxidative phosphorylation, a key factor in the poor response to conventional therapies in aggressive BC subtypes. The study uncovers a novel tumor-supportive role of USP22 in sustaining cellular respiration, which contributes to the drug-tolerant behavior of HER2+-BC and TNBC cells. This highlights USP22 as a potential therapeutic target, offering new avenues to optimize standard treatments and address the aggressiveness of these malignancies.
2023-12-31 | E-MTAB-13577 | biostudies-arrayexpress
Project description:Mouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation. In order to understand the transcriptional program underlying this biological defect, whole genome expression analysis was performed. E14 mESCs were infected with lentivirus containing shRNA targeting Usp22 or control (Luc). RNA was extracted from both samples and subjected to expression analysis by affymetrix array.
2013-05-15 | E-GEOD-42934 | biostudies-arrayexpress
Project description:USP22 plays oncogenic roles and in order to identify the molecular mechanism of USP22 to promote tumorigenesis, RNA-seq was performed on Huh7 cells with or without USP22.
2021-04-10 | GSE171225 | GEO
Project description:Mouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation. In order to understand the transcriptional program underlying this biological defect, whole genome expression analysis was performed.
2013-05-15 | GSE42934 | GEO
Project description:SAGA is a modular cofactor complex that is essential for eukaryotic transcription. SAGA’s complement of ~20 proteins exist within four structurally and functionally distinct modules, two of which are catalytic. Within the KAT module, GCN5 acetylates histone tails, leading to increased chromatin accessibility and bromodomain protein recruitment. The DUB module contains the ubiquitin hydrolase USP22. In yeast, the USP22 ortholog deubiquitylates H2B, resulting in Pol II S2 phosphorylation and subsequent transcriptional elongation. We report here that metazoan SAGA, and USP22 specifically, are required at a more proximal stage in activator-driven transcription, i.e. pre-initiation complex (PIC) assembly. A combination of genome-wide and proteomic analyses revealed that H2B deubiquitylation is not linked to USP22-dependent transcription. Instead, USP22 controls Mediator tail subunit ubiquitylation. Mechanistically, USP22 controls loading of Mediator tail and GTFs onto promoters, with Mediator core recruitment being USP22-independent. These findings place human SAGA function at the earliest steps in activator-driven transcription.
2021-04-12 | GSE158108 | GEO