Differential gene expression analysis were performed between Pitx1 silenced SCC cells and controls in two independent SCC lines Overall design: Compared control and Pitx1 deficient cells to define gene sets control by Pitx1 in SCCs.
De Novo PITX1 Expression Controls Bi-Stable Transcriptional Circuits to Govern Self-Renewal and Differentiation in Squamous Cell Carcinoma.
Specimen part, Cell line, Subject
View SamplesPlasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices.
A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity.
No sample metadata fields
View SamplesObesity is strongly associated with the metabolic syndrome, a compilation of risk factors that predispose individuals to the development of cardiometabolic disease (CMD), i.e. cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Controlling or preventing the worldwide epidemic of metabolic syndrome requires novel interventions to address this substantial health challenge. The objective of this study was the identification of potential new targets for the simultaneous prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie T2DM and CVD, respectively. Therefore, we used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining data from two microarray experiments and two meta-analyses. In the microarray experiments we compared gene expression in white adipose tissue (WAT) of obese mice as well as aortae of obese and atherosclerotic mice to respective lean controls. Furthermore, we performed a meta-analysis of published microarrays investigating atherosclerotic vessels and included a published meta-analysis on T2DM into our analyses. We obtained a pool of thirty-four genes that were upregulated in 3 out of the 4 underlying databases. These included well-known as well as novel crucial molecules for treatment of T2DM and CVD. Macrophage metalloelastase 12 (MMP12) was found highly ranked in all analyses and, therefore, chosen for further validation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of MMP12 in obesity at mRNA, protein and, of note, activity levels. In conclusion, by this unbiased approach an interesting pool of potential molecular targets or biomarkers for treatment and prevention of CMD was identified with MMP12 being confirmed on multiple levels.
Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease.
Specimen part
View SamplesPurpose: The goals of this study were to identify preferential gene expression signatures that are unique to Tregs in neonatal skin relative to peripheral Tregs Methods: Tregs from telogen skin and SDLNs were purified by cell sorting (using the Treg GFP reporter mouse line Foxp3-DTR/GFP) to generate mRNA transcription profiles. Results: Transcriptional profiling revealed a unique neonatal skin Treg signature relative to SDLN Tregs Conclusion: Our study represents the first detailed analysis of the neonatal skin Treg transcriptome. Overall design: mRNA profiles of skin and SDLN Tregs isolated from 13 day old Foxp3-DTR/GFP mice.
Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin.
Age, Specimen part, Cell line, Subject
View SamplesLangerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC.
Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells.
Specimen part
View SamplesThe transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.
STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.
Specimen part
View SamplesSeveral functions have been suggested for the interferon induced transmembrane protein 1 (Iftitm1) gene in mammals. Originally it was identified as a member of a gene family that is highly inducible by type I and type II inteferons. Based on its expression during primordial germ CELl (PGC) specification it was suggested to be required for normal PGC migration. Ifitm1 targeted knockdown experiments in mouse embryos provided evidence that the gene might be necessary for normal somitogenesis. Finally, the complete deletion of the Ifitm gene cluster on mouse chromosome 7 revealed that the five deleted Ifitm1 genes are not essential for PCG migration and fertility. Here, we generated a novel targeted knockin allele of the Ifitm1 gene by replacing its coding region with a lacZ reporter gene to systematically reassess the suggested functions of this gene.
In vivo functional requirement of the mouse Ifitm1 gene for germ cell development, interferon mediated immune response and somitogenesis.
Sex, Age, Specimen part
View SamplesLipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders.
Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue.
Specimen part, Treatment
View SamplesA basal (MDAMB468) and luminal (ZR75-1) cell line were treated with DMSO or PKC412 for 6h Overall design: 2 DMSO and 3 PKC412 treated samples for each cell line
Targeting a cell state common to triple-negative breast cancers.
No sample metadata fields
View SamplesPoorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas.
Gene expression profiling associated with the progression to poorly differentiated thyroid carcinomas.
Sex, Age, Specimen part
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