Vitiligo 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 SamplesAlterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility).
Differential RNAs in the sperm cells of asthenozoospermic patients.
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View SamplesThe nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Overall design: RNA profiles in wild-type and Taf4-/- livers by deep sequencing
TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.
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View SamplesMice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.
Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sex, Subject
View SamplesEpigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sex, Subject
View SamplesThe adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and stemcellness has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells.
Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype.
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View SamplesIn pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particulary involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases.
Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition.
Sex, Specimen part
View SamplesLhx8 is a member of the LIM-homeobox transcription factor family and preferentially expressed in oocytes and germ cells within the mouse ovary. We discovered that Lhx8 knockout females lose oocytes within 7 days after birth. At the time of birth, histological examination shows that Lhx8 deficient (Lhx8(-/-)) ovaries are grossly similar to the newborn wild type ovaries. Lhx8(-/-) ovaries fail to maintain the primordial follicles and the transition from primordial to growing follicles does not occur. Lhx8(-/-) ovaries misexpress oocyte-specific genes such as Gdf9, Pou5f1, and Nobox. Very rapid loss of oocytes may partly be due to drastic the down-regulation of Kit and Kitl in Lhx8(-/-) ovaries. We compared Lhx8(-/-) and wild-type ovaries using Affymetrix 430 2.0 microarray platform. Eighty (44%) of 180 of the genes down-regulated more than 5-fold in Lhx8(-/-) ovaries were preferentially expressed in oocytes, whereas only 3 (2%) of 146 genes up-regulated more than 5-fold in the absence of Lhx8 were preferentially expressed in oocytes. In addition, the comparison of genes regulated in Lhx8(-/-) and Nobox(-/-) newborn ovaries discovered a common set of 34 genes whose expression level is affected in both Lhx8 and Nobox deficient mice. Our findings show that Lhx8 is a critical factor for maintenance and differentiation of the oocyte during early oogenesis and it acts in part by down-regulating the Nobox pathway.
Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival.
Sex, Age, Specimen part
View SamplesNobox is a homeobox gene expressed in oocytes and critical in oogenesis. Nobox deficiency leads to rapid loss of postnatal oocytes. Early oocyte differentiation is poorly understood. We hypothesized that lack of Nobox perturbs global expression of genes preferentially expressed in oocytes as well as microRNAs. We compared Nobox knockout and wild type ovaries using Affymetrix 430 2.0 microarray platform. We discovered that 28 out of 38 (74%) of the genes down-regulated more than five fold in the absence of Nobox were preferentially expressed in oocytes, while only 5 out of 33 (15%) of genes up-regulated more than five fold in the absence of Nobox, were preferentially expressed in oocytes. Protein binding microarray helped identify nucleotide motifs that NOBOX binds, and that several down-regulated genes contain within putative promoter regions. MicroRNA population in newborn ovaries deficient of Nobox, was largely unaffected. Genes whose proteins are predicted to be secreted, but previously unknown to be significantly expressed in early oogenesis, were down regulated in Nobox knockouts and included astacin-like metalloendopeptidase (Astl), Jagged 1 (Jag1), oocyte secreted protein 1 (Oosp1), fetuin beta (Fetub) and R-spondin 2 (Rspo2). In addition, pluripotency associated genes, Pou5f1 and Sall4 are drastically down-regulated in Nobox deficient ovaries, while testes determining gene Dmrt1 is over-expressed. Our findings indicate that Nobox is likely an activator of oocyte-specific gene expression, and suggest that oocyte plays an important role in suppressing expression of male determining genes such as Dmrt1.
Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival.
Sex, Age, Specimen part
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