Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hi CX3CR1hi (CD11b+CD103-) cells account for 80% of mouse colonic lamina propria (cLP) MHC-IIhi cells. Both CD11c+ and CD11c- cells within this population were identified as MPs based on multiple criteria, including a MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs, based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+ DCs and CD103-CX3CR1intCD11b+ DCs. In non-inflammatory conditions, Ly6Chi monocytes differentiated primarily into CD11c+, but not CD11c- MPs. In contrast, during colitis, Ly6Chi monocytes massively invaded the colon and differentiated into pro-inflammatory CD103-CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS and TNF. These findings demonstrate the dual capacity of Ly6Chi blood monocytes to differentiate into either regulatory MPs or inflammatory DCs in the colon, and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.
Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon.
No sample metadata fields
View SamplesLung cancer is a highly malignant tumor and the majority of cancer-related deaths are due to metastasis. The tumor microenvironment (TME) plays a fundamental role in the metastatic spread of tumor cells. Among other stromal cells, mesenchymal stem cells (MSCs) are known to be present within the TME and to be involved in cancer progression. However the majority of previous studies have been performed on bone marrow-derived MSCs. To investigate the role of the TME on the pulmonary MSC phenotype, we compared the expression profile of paired MSCs isolated from lung tumor (T-) and normal adjacent tissues (N-) from lung carcinoma patients.
Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis.
Specimen part, Disease stage, Subject
View SamplesStem cells, with their potential to generate different lineages, could offer a solution by replacing damaged or lost cells within the inner ear. We have shown that human embryonic stem cells can be induced to differentiate into otic progenitors, and then into hair cell-like cells and neurons that display expected electrophysiological properties. More importantly, once these otic progenitors are transplanted into animals with induced hearing loss, they differentiate and elicit a significant recovery of auditory function. The generation of otic progenitors is triggered by FGF signalling. In this dataset we have analysed the global gene expression profile of undifferentiated hESCs and compared with cultures that have been treated with FGF3 and 10, the two ligands involved in otic induction, or cultures that have been allowed to differentiate under basal conditions without FGF (DFNB).
Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.
Cell line, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology.
Specimen part, Disease, Subject
View SamplesIn order to explore molecules whose expression is controlled by Slc39a13, we investigated gene expression profiling of primary chondrocyte isolated from wild-type and Slc39a13 knockout mice.
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
No sample metadata fields
View SamplesIn order to explore molecules whose expression is controlled by Slc39a13, we investigated gene expression profiling of primary osteoblast isolated from wild-type and Slc39a13 knockout mice.
The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.
No sample metadata fields
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 SamplesObesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein (HSD) or that has been supplemented with a rich source of saturated fat (HFD). These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline, such as decreased climbing ability. We subjected Oregon-R-C flies to variants of the HSD, HFD, or normal (control) diet (ND), followed by a total RNA extraction from fly heads of each diet group for the purpose of Poly-A selected RNA-Sequencing. We targeted at least 50 million paired-end, stranded reads of 75 basepairs in size, and analyzed 4 biological replicates per dietary condition. Our objective was to identify the effects of obesogenic diets on transcriptome patterns, how they differed between obesogenic diets, and identify genes that may relate to pathogenesis accompanying an obesity-like state. Functional annotation and enrichment analysis among genes whose expression was significantly affected by the obesogenic diets indicated an overrepresentation of genes associated with immunity, metabolism, and hemocyanin in the HFD group, and CHK, cell cycle activity, and DNA binding and transcription in the HSD group. Heat map representation of genes affected by both diets illustrated a large fraction of differentially expressed genes between the two diet groups. Diets high in sugar and diets high in fat both have notableeffects on the Drosophila transcriptome in head tissue. The impacted genes, and how they may relate to pathogenesis in the Drosophila obesity-like state, warrant further experimental investigation. Our results also indicate differences in the effects of the HFD and HSD on expression profiles in head tissue of Oregon-R-C flies, despite the reportedly similar phenotypic impacts of the diets. Overall design: Flies were reared on one of three diets (high fat, high sugar, or normal). 6 replicates, with twenty flies each, from each diet treatment were collected for a total of 18 samples. The heads of the flies were then obtained, and RNA extracted from each of those samples. 4 of the RNA samples from each diet group (12 samples total) were sequenced.
RNA-Sequencing of <i>Drosophila melanogaster</i> Head Tissue on High-Sugar and High-Fat Diets.
Specimen part, Subject
View SamplesWTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53 and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell cycle arrest, apoptosis, and p53-target gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.
The WTX tumor suppressor enhances p53 acetylation by CBP/p300.
Cell line
View SamplesEffect of absence of interaction with MHC class II on memory CD4 T cells
Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function.
Sex, Specimen part
View Samples