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Mus musculus
3 Downloadable Samples
Illumina HiSeq 1000
Description
Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30?/?), we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding g-Sarcoglycan (SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the cerebrovascular Sarcoglycan complex (SGC) and showed the presence of a-, ß-, d-, ?-, e- and ?- SG, as well as Sarcospan. Altogether, our results suggest that the Sarcoglycan complex is present in the cerebrovascular system, and that expression of one of its members, g-Sarcoglycan, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. Overall design: Comparison of 3-month-old Cx30 deleted mice against WT genetic background.
Publication Title
The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 16 Downloadable Samples
Porcine Gene 1.0 ST Array (porgene10st)
Description
GLP-1 agonists are potent glucose-lowering agents, however, their effect on adolescent organisms needs to be clarified
Publication Title
Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD146low/negCD166low/negCD73+CD44lowBMPR1B+) distinguishing the earliest cartilage committed cells (pre-chondrocytes) at 5-6 weeks of development; pellet assays confirmed these cells as functional, chondrocyte-restricted progenitors. Flow cytometry, qPCR and immunohistochemistry at 17 weeks revealed that the superficial layer of peri-articular chondrocytes was enriched in cells with this surface phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166negBMPR1B+ putative pre-chondrocytes. Functional characterization confirmed these cells as cartilage-committed, chondrocyte progenitors. The identification of a specific molecular signature for primary cartilagecommitted progenitors may provide essential knowledge for the generation of purified, clinically relevant cartilage cells from PSCs.
Publication Title
Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human epidermal keratinocytes were treated with 25 ng.ml EphB2 or EFNA4, both as-Fc conjugates (Sigma).
Publication Title
Eph-2B, acting as an extracellular ligand, induces differentiation markers in epidermal keratinocytes.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Both ephrins and their receptors are membrane bound, restricting their interactions to the sites of direct cell-to-cell interfaces. They are widely expressed, often co-expressed and regulate developmental processes, cell adhesion, motility, survival, proliferation, and differentiation. Both tumor suppressor and oncogene activities are ascribed to EFNs and Ephs in various contexts. A major conundrum regarding the EFN/Eph system concerns their large number and functional redundancy, given the promiscuous cross-activation of ligands and receptors and the overlapping intracellular signaling pathways. To address this issue, we treated human epidermal keratinocytes with 5 EFNAs individually and defined the transcriptional responses in the cells. We found that a large set of genes is coregulated by all EFNAs. However, while the responses to EFNA3, EFNA 4 and EFNA 5 are identical, the responses to EFNA1 and EFNA2 are characteristic and distinctive. All EFNAs induce epidermal differentiation markers and suppress cell adhesion genes, especially integrins. Ontological analysis shows that all EFNAs induce cornification and keratin genes, while suppressing wound-healing associated, signaling, receptor and ECM associated genes. Transcriptional targets of AP1 are selectively suppressed by EFNAs. EFNA1 and EFNA2, but not the EFNA3, EFNA4, EFNA5 cluster, regulate the members of the ubiquitin-associated proteolysis genes. EFNA1 specifically induces collagen production. Our results demonstrate that the EFN-Eph interactions in the epidermis, while promiscuous, are not redundant but specific. This suggests that different members of the EFN/Eph system have specific, clearly demarcated functions.
Publication Title
Specific and shared targets of ephrin A signaling in epidermal keratinocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. Reaching confluency did not affect adhesion and ECM proteins. Lipid metabolism and steroid metabolism were induced by confluency and by JNK inhibition, respectively. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis.
Publication Title
Keratinocyte detachment-differentiation connection revisited, or anoikis-pityriasi nexus redux.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 13 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin (DMD) gene. The absence of dystrophin protein leads to progressive muscle weakness and wasting, disability and death. To establish a tailored large animal model of DMD, we deleted DMD exon 52 in male pig cells by gene targeting and generated offspring by nuclear transfer. DMD pigs exhibit absence of dystrophin in skeletal muscles, increased serum creatine kinase levels, progressive dystrophic changes of skeletal muscles, impaired mobility, muscle weakness, and a maximum life span of 3 months due to respiratory impairment. To address the accelerated development of muscular dystrophy in DMD pigs as compared to human patients, we performed a genome-wide transcriptome study of M. biceps femoris samples from 2-day-old and 3-month-old DMD and age-matched wild-type pigs. The transcriptome changes in 3-month-old DMD pigs were in good accordance with the findings of gene expression profiles in human DMD, reflecting the processes of degeneration, regeneration, inflammation, fibrosis, and impaired metabolic activity. The transcriptome profile of 2-day-old DMD pigs pointed towards increased protein and DNA catabolism, reduced extracellular matrix formation and cell proliferation and showed similarities with transcriptome changes induced by exercise injury in muscle. Our transcriptome studies provide new insights into congenital changes associated with dystrophin deficiency and secondary complications arising during postnatal development. Thus the DMD pig is a useful model to determine the hierarchy of physiological derangements in dystrophin-deficient muscle.
Publication Title
Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Cultured keratinocytes treated with TNFa in the presence or absence of NFkB inhibitor; time course 1, 4, 24 & 48 hrs.
Publication Title
Pathway-specific profiling identifies the NF-kappa B-dependent tumor necrosis factor alpha-regulated genes in epidermal keratinocytes.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE2822- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Cultured epidermal keratinocytes treated with OsM 1, 4, 24 & 48hrs, and Skinethic epidermal substitutes treated 1, 4, 24, 48h & 7days, each with untreated control
Publication Title
Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions.
Publication Title
Transcriptional profiling defines the roles of ERK and p38 kinases in epidermal keratinocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples