Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research.
MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.
Time
View SamplesMonoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. Overall design: PolyA RNA purification and subsequent high-throughput sequencing were performed on two independent B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus, and on two independent fibroblast clonal cell lines, derived from 129S1/Sv x CAST/EiJ F1 and immortalized with SV40.
Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.
No sample metadata fields
View SamplesCadmium sulfide quantum dots (CdS QDs) are widely used in novel equipment. The relevance of the research lies in the need to develop risk assessments for nanomaterials, using as basis a model plant species.
Genome-wide approach in Arabidopsis thaliana to assess the toxicity of cadmium sulfide quantum dots.
Specimen part, Treatment
View SamplesGene expression variation upon folate deficiency and repletion in human foreskin keratinocytes immortalized by HPV16E6E7 Overall design: Effects of folate modulation on several cellular events such as DNA stability
Folate Repletion after Deficiency Induces Irreversible Genomic and Transcriptional Changes in Human Papillomavirus Type 16 (HPV16)-Immortalized Human Keratinocytes.
Specimen part, Subject
View SamplesAnalysis of Allelic bias in clonal lymphoblastoid cells. Abstract: In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ~20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. Overall design: Poly A purified total RNA was used for library construction using a method described by Parkhomchuk et. al. NAR 2009. The library was strand-specific but the pipeline for data analysis does not assume the library is strand-specific.
Chromatin signature of widespread monoallelic expression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesCD34+ cord blood hematopoietic progenitors were expanded in vitro as previously described (Balan et al., J Immunol, 2014) and then differentiated on a mixed feeder layer of OP9 cells expressing or not the Notch ligand Delta-like 1, with FLT3-L, TPO and IL-7. At the end of the cultures, single live Lin- HLA-DR+ cells were index sorted in 96-well plates containing lysis buffer, and snap frozen. Four putative cell types were sorted according to their expression patterns of key combinations of cell surface markers: putative pDCs, putative cDC1s, putative pre-cDC2s and putative cDC2s. Single cell RNA-sequencing libraries were subsequently generated for 90 single cells and 6 control wells using an adaptation of Smart-Seq2 (Villani et al., Science, 2017). Cells were sequenced at a depth of 1-3M reads/cell. Overall design: A total of 90 single cells and 6 controls from one culture were processed using a protocol adapted from Smart-Seq2 protocol (Villani et al., Science, 2017), which allows for the generation of full-length single cell cDNA, and sequencing libraries were generated using Illumina Nextera XT DNA library preparation kit. A few samples (10) were profiled but excluded from the processed data since they were either bulk (5) or blank (1) control samples or excluded due to QC (4). Therefore, there are 86 samples included here.
Large-Scale Human Dendritic Cell Differentiation Revealing Notch-Dependent Lineage Bifurcation and Heterogeneity.
Specimen part, Subject
View SamplesNovel strategies are needed to modulate -cell differentiation and function as potential -cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on cells was incompletely defined. We find that isoxazole largely induced genes that support neuroendocrine and -cell phenotypes, and suppressed a set of genes important for proliferation. Isoxazole alters -cell metabolites and protects glucose-responsive signaling pathways under lipotoxic conditions. Finally, we show that isoxazole improves glycemia in a mouse model of -cell regeneration. Isoxazole is a prime candidate for altering cell fate in different contexts.
Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.
Specimen part
View Samples