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GSE89827
Homo sapiens
8 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
Publication Title
Human Lacrimal Gland Gene Expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic and genomic analyses of RNA polymerase II-pausing factor in regulation of mammalian transcription and cell growth.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Many mammalian genes are occupied by paused RNA polymerase II (pol II) at promoter-proximal regions on both sides of transcription start sites (TSSs). However, the consequences of pol II pausing on gene expression and cell biology are not fully understood. Here we report that genetic ablation of the b subunit of mouse negative elongation factor (Nelf-b), a key pol II-pausing factor, results in slower progression at multiple cell cycle stages and increased apoptosis. Consistently, a whole-genome analysis indicates that growth and cell death-related genes are highly enriched among the direct target genes of Nelf-b. In particular, Nelf-b deletion increases pol II density in the promoter-distal region of stress response genes and their overall expression levels in the absence of any external stress signals. In addition, our work also reveals a previously unappreciated role of Nelf-b role in curbing TSS-upstream transcription of many mammalian genes. We suggest that Nelf-mediated pol II pausing balances the cellular needs for growth/survival and stress response by preventing excessive basal transcription of stress-induced genes.
Publication Title
Genetic and genomic analyses of RNA polymerase II-pausing factor in regulation of mammalian transcription and cell growth.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Inborn errors of lipid metabolism illustrate the importance of proper milk fat oxidation in newborn mammals. In the liver, a remarkable lipid catabolic competence is present at birth; however, it is unclear how this critical trait is acquired and regulated. In this work, we found that the genes required for milk lipid catabolism are already transcribed before birth in the term fetus (E19.5) and controlled by the peroxisome-proliferator activated receptor alpha (PPAR) in mouse liver. The developmental activity of PPAR strongly regulates fatty acid oxidation genes. Two days after birth (P2), during milk suckling, PPAR-null mice develop a congenital steatosis and milk protein oxidation is de-repressed to fuel an alternative energy pathway that maintains glucose homeostasis and postnatal growth. Our results demonstrate for the first time, the developmental role of PPAR in regulating the metabolic ability to use maternal milk as fuel in the early days of life.
Publication Title
Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Inborn errors of lipid metabolism illustrate the importance of proper milk fat oxidation in newborn mammals. In the liver, a remarkable lipid catabolic competence is present at birth; however, it is unclear how this critical trait is acquired and regulated. In this work, we found that the genes required for milk lipid catabolism are already transcribed before birth in the term fetus (E19.5) and controlled by the peroxisome-proliferator activated receptor alpha (PPAR) in mouse liver. The developmental activity of PPAR strongly regulates fatty acid oxidation genes. Two days after birth (P2), during milk suckling, PPAR-null mice develop a congenital steatosis and milk protein oxidation is de-repressed to fuel an alternative energy pathway that maintains glucose homeostasis and postnatal growth. Our results demonstrate for the first time, the developmental role of PPAR in regulating the metabolic ability to use maternal milk as fuel in the early days of life.
Publication Title
Glucocorticoid receptor-PPARα axis in fetal mouse liver prepares neonates for milk lipid catabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally, is influenced by both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as a candidate COPD susceptibility gene based on genetic association studies, with IRP2 increased in the lungs of COPD patients. Here we demonstrate that mice deficient in IRP2 are protected from cigarette smoke (CS)-induced COPD. Using RIP-Seq, RNA-Seq, gene expression and pathway analysis, we identify IRP2 as a regulator of mitochondrial function in the lung. We show that an increase in IRP2 results in a cytochrome c oxidase (COX)-dependent alteration in oxidative capacity and mitochondrial-iron dysfunction involving frataxin. We demonstrate that mice with impaired COX or frataxin activity have altered responses to CS and show that overexpressing IRP2 in vivo alters mitochondrial dynamics. These data suggest a critical role of the mitochondria-iron axis in mediating the pathogenesis of COPD.
Publication Title
Mitochondrial iron chelation ameliorates cigarette smoke-induced bronchitis and emphysema in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
DNA microarray technology is a powerfull tool for genome-wide gene expression analysis of biological samples. Here we review the methodology for expression profiling analysis of skin tissue or purified keratinocytes from mice. We explained the methodology and protocols for RNA preservation and purification, RNA quality and integrity tests, and DNA microarray technology types that can be used. Furthermore, using a dataset of mice samples, we explained how to perform chip raw data preprocessing and normalization, differential expression analysis, as well as gene-clustering and funcional analysis of gene deregulation.
Publication Title
Gene expression profiling of mouse epidermal keratinocytes.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided in two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer. We have previously reported that combined Rb1-Rbl1 and Rb1-E2F1 ablation in epidermis produces important alterations in epidermal proliferation and differentiation, leading to tumor development. However, the possible roles of E2F4 in this context are still to be determined. Here we show the absence of any discernible phenotype in the skin of mice lacking of E2F4. In contrast, the inducible loss of Rb1 in the epidermis of E2F4-null mice produced multiple skin abnormalities including altered differentiation and proliferation, spontaneous wounds, carcinoma in situ development and stem cell perturbations. All these phenotypic alterations are associated with extensive gene expression changes, the induction of c-myc and the Akt activation. Moreover, the whole transcriptome analyses in comparison with previous models generated also revealed extensive changes in multiple repressive complexes and in transcription factor activity. These results point to E2F4 as a master regulator in multiple steps of epidermal homeostasis in Rb1 absence.
Publication Title
Deregulation of the pRb-E2F4 axis alters epidermal homeostasis and favors tumor development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of catenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs.
Publication Title
E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played non redundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factorb family ligand inhibin bA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
Publication Title
The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples