The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alphacatenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that -catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis.
Specimen part
View SamplesPRDM proteins belong to the SET domain protein family, which is involved in the regulation of gene expression. Although few PRDM members possess histone methyltransferase activity, the molecular mechanisms by which the other members exert transcriptional regulation remain to be delineated. In this study, we find that Prdm5 is highly expressed in mouse embryonic stem (mES) cells and exploit this cellular system to characterize molecular functions of Prdm5. By combining proteomics and next-generation sequencing technologies, we identify Prdm5 interaction partners and genomic occupancy. We demonstrate that although Prdm5 is dispensable for mES cell maintenance, it directly targets genomic regions involved in early embryonic development and affects the expression of a subset of developmental regulators during cell differentiation. Importantly, Prdm5 interacts with Ctcf, cohesin, and TFIIIC and cooccupies genomic loci. In summary, our data indicate how Prdm5 modulates transcription by interacting with factors involved in genome organization in mouse embryonic stem cells. Overall design: For each condition (ATRA-induced differentiation model and LIF cytokine deprivation) three replicate are available for both Prdm5 wt mES cells and Prdm5 KO mES cells, for a total of 12 samples
Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells.
No sample metadata fields
View SamplesCXCL5, a strong neutrophil-chemoattractant, has been reportet to be expressed in different cancer entities with diverse outcomes in disease progression. Contradictory outcome in disease progression in different tumor entities might be explained by a tumor type specific expression pattern of chemokines, chemokine receptors and growth factors that act in concert with CXCL5. This study evaluates the impact of CXCL5 expression on the tumor mircoenvironment in a syngeneic mouse melanoma model. Overall design: 105 B16F1 and B16F1-CXCL5 murine melanoma were injected intradermally into the flank skin of C57BL/6 J mice. Primary tumors were grown up to 250-350mm³, excised, snap frozen and then processed for RNA sequencing.
CXCL5 as Regulator of Neutrophil Function in Cutaneous Melanoma.
Specimen part, Treatment, Subject
View SamplesRRP1B is a breast cancer metastasis suppressor that interacts with various regulators of gene transcription
Metastasis-associated protein ribosomal RNA processing 1 homolog B (RRP1B) modulates metastasis through regulation of histone methylation.
Specimen part, Cell line
View SamplesPRDM proteins are tissue specific transcription factors often deregulated in diseases, particularly in cancer where different members have been found to act as oncogenes or tumor suppressors. PRDM5 is a poorly characterized member of the PRDM family for which several studies have reported a high frequency of promoter hypermethylation in cancers of gastrointestinal origin. We report here the characterization of Prdm5 knockout mice in the context of intestinal carcinogenesis. We demonstrate that loss of Prdm5 increases the number of adenomas throughout the murine small intestine on an ApcMin background. By genome-wide ChIP-seq and transcriptome analyses we identify loci encoding proteins involved in metabolic processes as prominent PRDM5 targets and characterize monoacylglycerol lipase (Mgll) as a direct PRDM5 target in human colon cancer cells and in Prdm5 mutant mouse intestines. Moreover, we report the downregulation of PRDM5 protein expression in human colon neoplastic lesions. In summary, our data provide the first causal link between Prdm5 loss and intestinal carcinogenesis and uncover an extensive and novel PRDM5 target repertoire likely facilitating the tumor suppressive functions of PRDM5.
Prdm5 suppresses Apc(Min)-driven intestinal adenomas and regulates monoacylglycerol lipase expression.
No sample metadata fields
View SamplesThe Affymetrix Human Gene 2.0 ST array was used to measure differential expression of RNA isolated from normal and Diamond Blackfan anemia (DBA) erythroid progenitors after ex vivo expansion of circulating, peripheral blood derived hematopoietic stem cells under erythroid growth conditions. The gene-level probe summaries reported in this series were computed using RMA as implemented in the Bioconductor package Oligo v1.36.1.
Molecular convergence in ex vivo models of Diamond-Blackfan anemia.
Specimen part
View SamplesNdn is a candidate metastasis suppressor gene that has been reported to regulate transcription.
Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc.
Cell line
View SamplesWe profiled transcripts from sorted phloem cells of wild-type and apl mutants to identify the genes regulated by APL in phloem.
Plant development. Arabidopsis NAC45/86 direct sieve element morphogenesis culminating in enucleation.
Specimen part
View SamplesWe have analyzed 2 normal B cells isolated from peripheral blood and 5 CLL specimens with affy 133A microarray for expression.
Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sex, Disease, Subject, Time
View Samples