Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overexpression of Cbx4 wild type and of a Cbx4 sumoylation mutant in human epidermal stem cells

ABSTRACT: Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex-1 (PRC1)-associated protein, maintains human epidermal stem cells slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its anti-senescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors, such as Ezh2, Dnmt1, and Bmi1, to prevent the activate stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation. Primary human keratinocytes were infected with control vector pBABE, Cbx4 wildtype and a Sumoylation mutant version of Cbx4 (the two Sumo Interaction Motifs were deleted), both fused to a Estrogen Receptor to render their activaty inducible by addition of 4OHT to the media. Cells were cultured for 5 days (after infection and selection) under 4OHT treatment, after which total RNA was collected.

ORGANISM(S): Homo sapiens

SUBMITTER: Salvador Benitah

PROVIDER: E-GEOD-31094 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Knockdown and Overexpression of Cbx4 wild type and of a Cbx4 chromodomain mutant in human epidermal stem cells

Project description:Human epidermal stem cells transit from a slow cycling to an actively proliferating state to contribute to homeostasis. Both stem cell states differ in their cell cycle profiles but must remain guarded from differentiation and senescence. Here we show that Cbx4, a Polycomb Repressive Complex-1 (PRC1)-associated protein, maintains human epidermal stem cells slow-cycling and undifferentiated, while protecting them from senescence. Interestingly, abrogating the polycomb activity of Cbx4 impairs its anti-senescent function without affecting stem cell differentiation, indicating that differentiation and senescence are independent processes in human epidermis. Conversely, Cbx4 inhibits stem cell activation and differentiation through its SUMO ligase activity. Global transcriptome and chromatin occupancy analyses indicate that Cbx4 regulates modulators of epidermal homeostasis and represses factors, such as Ezh2, Dnmt1, and Bmi1, to prevent the activate stem cell state. Our results suggest that distinct Polycomb complexes balance epidermal stem cell dormancy and activation, while continually preventing senescence and differentiation. Primary human keratinocytes were infected with control vector pBABE, Cbx4 wildtype and a chromodomain mutant version of Cbx4 (F11A and W35L), both fused to a Estrogen Receptor to render their activaty inducible by addition of 4OHT to the media. Cells were cultured for 5 days (after infection and selection) under 4OHT treatment, after which total RNA was collected. For the knockdown, the pRetroSuperPuro was used as a control vector, in which a shRNA sequence for Cbx4 was introduced to interfere with Cbx4 expression. Cell were cultured in the same way as for the overexpression experiments.

2011-08-01 | E-GEOD-31093 | biostudies-arrayexpress

Knockdown and Overexpression of Cbx4 wild type and of a Cbx4 chromodomain mutant in human epidermal stem cells

2011-08-02 | GSE31093 | GEO

Overexpression of Cbx4 wild type and of a Cbx4 sumoylation mutant in human epidermal stem cells

2011-08-02 | GSE31094 | GEO

Polycomb Repressive Complex 1 subunit Cbx4 positively regulates effector responses in CD8 T cells

Project description:Cytotoxic T lymphocyte (CTL) differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Fully uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. Here, we show that Polycomb Repressive Complex (PRC)1 subunit Chromobox (Cbx)4 favors effector CTL differentiation in murine model. Cbx4 deficiency in CTLs induced transcriptional signature and phenotype of memory cells, increasing the memory CTL population during acute viral infection. It has been previously shown that besides binding to H3K27me3 through its chromodomain, Cbx4 function as a SUMO E3 ligase in a SUMO interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in a SIM-dependent way and partially through its chromodomain. Our data revealed a novel role of a Polycomb group protein Cbx4 controlling CTL differentiation and indicates the SUMOylation as a key molecular mechanism connected to chromatin modification in this process.

2023-07-10 | GSE236487 | GEO

Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

Project description:CBX4, a component of polycomb repressive complex 1 (PRC1), plays important roles in the maintenance of cell identity and organ development through epigenetic silencing. However, whether CBX4 regulates the homeostasis of human stem cells remains unclear. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein is decreased in aged hMSCs, and targeted CBX4 knockout in young hMSCs results in destabilized nucleolar heterochromatin, increased ribosome biogenesis and protein translation, and accelerated cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin and heterochromatin organization associated protein KAP1 at nucleolar rDNA, limiting the excessive expression of rRNAs. Importantly, overexpression of CBX4 alleviates physiological hMSC aging and attenuates the development of posttraumatic osteoarthritis in mice. Taken together, our findings reveal a novel role of CBX4 in counteracting senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.

2019-01-19 | GSE125320 | GEO

Safeguarding nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis

Project description:Chromobox homolog 4 (CBX4), a component of polycomb repressive complexes 1 (PRC1), plays important roles in the maintenance of cell identity and organism development through epigenetic silencing. However, it remains unclear whether CBX4 regulates the homeostasis of human stem cells. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein decreases in aged hMSCs, and targeted knockout of CBX4 in young hMSCs destabilizes nucleolar heterochromatin, increases ribosome biogenesis, and accelerates cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting fibrillarin at nucleolar rDNA repeats, limiting excessive expression of rRNAs. Importantly, overexpression of CBX4 expression alleviates physiological hMSC aging as well as attenuates the development of post-traumatic osteoarthritis in mice. Taken together, our study uncovers a novel role of CBX4 in counteracting senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.

2019-07-13 | GSE117084 | GEO

RNA sequencing of slow-and fast-cycling epidermal stem cells vs hair follicle stem cells in young vs old mice

Project description:This study was performed to compare transcriptomic changes in the heterogeneous mouse skin epidermal stem cells and hair follicle stem cells (HFSC) populations during chronological aging. Slow-cycling stem cells (label retaining cells, LRCs), fast-cycling stem cells (non-label retaining cells, nLRCs) and hair follicle stem cells express unique gene signatures in young age (2 months old) and have independent stem cell identities. The changes in aging stem cells lineage identities have been a topic of discussion and here we examined if distinct stem cells cycling speed affects their aging process by comparing the transcriptomes of slow-and fast-cycling epidermal stem cells. Our data indicates the loss of unique stem cell identities in aging slow or fast-cycling epidermal stem cells or HFSC at 2 years of age with intermediary effects seen at 1.5 year old.

2022-10-01 | GSE185087 | GEO

Knockdown and Overexpression of Cbx4 wild type, Cbx4 chromodomain mutant, and Cbx4 sumoylation mutant in human epidermal stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE31093: Knockdown and Overexpression of Cbx4 wild type and of a Cbx4 chromodomain mutant in human epidermal stem cells GSE31094: Overexpression of Cbx4 wild type and of a Cbx4 sumoylation mutant in human epidermal stem cells Refer to individual Series

2011-08-02 | E-GEOD-31147 | biostudies-arrayexpress

Contribution of CBX4 to cumulus oophorus cell phenotype in mice, and attendant effects in cumulus cell cloned embryos

Project description:Cumulus oophorus cells play an essential role in oocyte development. CBX4 is a member of the Polycomb complex, which plays a role in regulating cellular differentiation. We used siRNA mediated knockdown of Cbx4 expression followed by Affymetrix array analysis to evaluate the role of CBX4 in cumulus cell differentiated state.

2014-04-29 | E-GEOD-46565 | biostudies-arrayexpress

Multiple Arkadia/RNF111 structures coordinate its Polycomb body association and transcriptional control

Project description:The RING domain protein Arkadia/RNF111 is a ubiquitin ligase in the transforming growth factor beta (TGFβ) pathway. We previously identified Arkadia as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). However, precisely how SUMO interaction contributes to the function of Arkadia was not resolved. Through analytical molecular and cell biology, we found that the SIMs share redundant function with Arkadia's M domain, a region distinguishing Arkadia from its paralogs ARKL1/ARKL2 and the prototypical SUMO-targeted ubiquitin ligase (STUbL) RNF4. The SIMs and M domain together promote both Arkadia's colocalization with CBX4/Pc2, a component of Polycomb bodies, and the activation of a TGFbeta pathway transcription reporter. Transcriptome profiling through RNA sequencing showed that Arkadia can both promote and inhibit gene expression, indicating that Arkadia's activity in transcriptional control may depend on the epigenetic context, defined by Polycomb repressive complexes and DNA methylation [Sun, Liu, and Hunter (2014) Mol Cell Biol 34(16):2981-2995].

2015-02-11 | GSE65796 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data