This SuperSeries is composed of the SubSeries listed below.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfr+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfra+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. Overall design: Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Myf5-CrE;mTmG embryos, were further fractionated based on the expression of PDGFRa, Itga7 and Myf5-cre (GFP). Total mRNA profiles from Myf5-cre(GFP)+PDGFRa+ and Myf5-cre(GFP)+PDGFRa-Itga7+ cells were generated by deep sequenceing
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
No sample metadata fields
View SamplesHistone methylation occurs on both lysine and arginine residues and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD domain (PHDUHRF1), an important regulator of DNA CpG methylation, as an unanticipated histone H3 unmodified arginine 2 (H3R2)-recognition modality. This conclusion is based on binding studies and co-crystal structures of the PHDUHRF1 bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarray and ChIP studies. Importantly, we show that UHRF1s ability to repress its direct target gene expression is dependent on PHDUHRF1 binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function.
PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression.
Specimen part, Cell line
View SamplesRPA12 is a subunit of RNA polymerase I.
Microarray data analyses of yeast RNA Pol I subunit RPA12 deletion strain.
No sample metadata fields
View SamplesWe hypothesized that gene expression in lungs of Fra-1+/+ and Fra-1-/- mice are divergent thus contributing fibrosis. More specifically, Fra-1-/- mice are increased susceptible to fibrosis. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Fra-1+/+ and Fra-1-/- mice at early time point.
Expression profiling of genes regulated by Fra-1/AP-1 transcription factor during bleomycin-induced pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling.
Cell line
View SamplesHuman prostate CWR22 OT-tumor cells were prospectively purified for expression of various stem cell markers (TRA-1-60/CD151/CD166/EpCAM/CD44/2-Integrin). Unsorted total tumor cells or the additional marker positive cells that do not manifest stem-like characteristics were used as control. All these cells were subjected to molecular profiling of total RNA expression and the fold change data are tabulated according to S/TFE of the purified cells in relation to their control.
Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling.
Cell line
View SamplesGlioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature it cannot be completely removed. We have recently shown that the WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is downregulated in glioblastoma and acts as strong tumor suppressor. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. MALAT1, a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knock-down of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation.
WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.
Specimen part, Cell line
View SamplesObjective: Conflicting evidence exists regarding the suppressive capacity of Tregs from the peripheral blood (PB) of patients with rheumatoid arthritis (RA). Our aim was to determine whether Tregs are intrinsically defective in RA using a wide range of read-out assays. Methods: CD3+CD4+CD25+CD127low Tregs from CD45RO+ and CD45RA+ compartments of PB from patients with RA and healthy controls (HC) were analysed for phenotype, cytokine expression profile (ex vivo and after in vitro stimulation), suppression of effector T-cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiling. Results: No differences were observed between patients with RA and HC regarding Treg frequency, ex vivo phenotype (CD4, CD25, CD127, CD39, CD161) or pro-inflammatory cytokine profile (IL-17, IFN-gamma, TNF-alpha). FOXP3 expression was increased in Tregs from RA blood. The ability of Tregs to suppress T-cell proliferation or cytokine (IFN-gamma, TNF-alpha) production upon co-culture with autologous CD45RO+ effector T-cells and monocytes was not significantly different between patients with RA and HC. CD45RO+ Tregs from RA blood showed a slightly impaired ability to suppress production of some cytokines/chemokines by autologous LPS-activated monocytes (IL-1-beta, IL-1Ra, IL-7, CCL3, CCL4), but this was not true for all patients and other cytokines/chemokines (TNF-alpha, IL-6, IL-8, IL-12, IL-15, CCL5) were suppressed in the majority of patients similarly to HC. Finally, gene expression profiling of CD45RA+ or CD45RO+ Tregs from PB revealed no statistically significant differences between patients with RA and HC. Conclusions: Our findings suggest that Tregs isolated from PB of patients with RA are not intrinsically defective.
Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid Arthritis.
Specimen part, Disease, Disease stage, Subject
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