High throughput massively parallel sequencing on mRNA libraries generated from cortices of bexarotene or vehicle treated APP/PS1 Overall design: Read counts analyzed for differential gene expression using edgeR
RNA-sequencing reveals transcriptional up-regulation of Trem2 in response to bexarotene treatment.
Specimen part, Cell line, Subject
View SamplesMuscle injury was elicited by cardiotoxin injection into the tibialis anterior muscle. Macrophages were isolated 2 days post-injury from the regenerating muscle.
Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration.
Specimen part
View SamplesTibialis anterior muscle was damaged by cardiotoxin injection and macrophage subsets were isolated and analyzed by gene expression analysis.
Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.
Time
View SamplesVitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuaLesionalparticipate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controLesionalof healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem celLesionalinto pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions.
Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients.
Specimen part
View SamplesSkeletal muscle regeneration is a highly dynamics process. The study aims at investigating gene expression by endothelial cells and satellite/myogenic cells during this process, in mouse, after a toxic injury
Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages.
Specimen part, Time
View SamplesBackground: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RAR expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RAR agonist with >20-fold selectivity over RAR and RAR. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RAR selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.
Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene.
Specimen part
View SamplesVCaP cells expressing inducible shRNAs for either ERG or a non-targeting control were treated with Doxycycline for 1, 3, 7 and 10 days prior to collection
TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation.
No sample metadata fields
View SamplesA transgenic TMPRSS2:ERG mouse model was engineered in FVB background and compared to its wildtype counterpart in the absence of any treatment This experiment is designed to look at ERG-dependent changes in phenotype and gene expression Overall design: A loxP-GFP-loxP-hERG exon 4-11 cassette was inserted into a BAC clone containing the TMPRSS2 locus using a recombineering kit. This modified BAC was used for pronuclear injection and generation of germline-transmitting mice. One line expressing high GFP was used for pronuclear injection of Cre protein and one sub-line that transmitted the TMPRSS2:ERG transgene into the germline was subsequently bred to homozygosity.
TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sex, Age, Specimen part, Disease stage
View SamplesBackground: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets.
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sex, Disease stage
View Samples