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SRP059699
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on Setdb1 roles in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. Ex vivo studies on isolated single myofibres showed that Setdb1 is required for muscle adult stem cells expansion following activation. In vitro studies in skeletal myoblasts confirmed that Setdb1 suppresses terminal myoblast differentiation. Genomic binding analyses showed a release of Setdb1 from the promoter of selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. Both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Together, our findings revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions and adult myogenesis. Overall design: RNA-seq of knockdown of Setdb1 in myoblast cells (C2C12).
Publication Title
Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The TAP transporter is responsible for transferring cytosolic peptides into the ER where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC surface expression and alters the presented peptide pattern. Using the TAP deficient cell line LCL721.174 and its TAP expressing progenitor cell line LCL721.45, we have identified and quantified more than 160 HLA ligands, 50 out of which were presented TAP independently. Peptides which were predominantly presented on the TAP deficient LCL721.174 cell line had a decreased MHC binding affinity according to their SYFPEITHI and BIMAS score. About half of the identified TAP independently presented peptides were not derived from signal sequences and may partly be generated by the proteasome. Furthermore, we have excluded that different HLA presentation ratios were due to varying expression of the respective protein or due to changes in the antigen loading complex. Features of TAP-independently presented peptides as well as proteasomal contribution to their generation provides an insight into basic immunological mechanisms.
Publication Title
Features of TAP-independent MHC class I ligands revealed by quantitative mass spectrometry.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn.
Publication Title
Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis!
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 32 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
An important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected.
Publication Title
Identifying significant temporal variation in time course microarray data without replicates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) overexpression on the gene expression profiles of tumors from MMTV-Neu mice. Hemizygous MMTV-Neu and MMTV-Spot14 mice were bred and 1 cm tumors from Neu control or Neu/Spot14 bitransgenic offspring were profiled using Affymetrix gene arrays. Tumors from Neu/Spot14 mice emerged significantly earlier than controls, but expressed many genes associated with lactogenic differentiation and were not highly metastatic. These results from the mouse model are consistent with observations from primary human breast tumors, which indicate that high Spot14 gene expression was directly correlated with a luminal subtype and a positive ER status. Overexpression of Spot14 in cultured mammary epithelial cells stimulated proliferation but not differentiation. Together, these data suggest that, in vivo, Spot14 is expressed in well-differentiated cells, and promotes the expansion of this population in the context of oncogenic signaling pathway activation.
Publication Title
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) loss on the gene expression profiles of tumors from MMTV-Polyomavirus middle-T antigen (PyMT) mice. MMTV-PyMT/S14-heterozygous mice were crossed with S14-heterozygous mice and 1 cm tumors from MMTV-PyMT control (wild-type S14) or MMTV-PyMT/S14-null offspring were profiled using Affymetrix gene arrays. Tumor latency was not different between groups; however, tumors lacking S14 grew significantly slower than control tumors. Loss of S14 also decreased the levels of de novo synthesized fatty acids in mammary tumors. In additional studies, performed on MMTV-Neu mice, we found that S14 overexpression was associated with increased tumor cell proliferation and elevated levels of tumor fatty acids. Gene expression profiling revealed that S14 loss and overexpression in mouse mammary tumors altered pathways associated with proliferation and metabolism. This study provides important information about the role of S14 in mammary tumorigenesis and tumor metabolism.
Publication Title
Modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) represent two major approaches for somatic cell reprogramming. However, little attention has been paid to the ability of these two strategies in rejuvenating cells from donors with aging associated syndrome. Here, we utilized telomerase deficient (Terc-/-) mice to probe this question. SCNT-derived embryonic stem cells (ntESCs) and iPSCs were successfully derived from second generation (G2) and third generation (G3) of Terc-/- mice, and ntESCs showed better differentiation potential and self-renewal ability. Telomeres lengthened extensively in cloned embryos while remained or slightly increased in the process of iPSCs induction. Furthermore, G3 ntESCs exhibited improvement of telomere capping function as evidenced by decreased signal free ends and chromosome end-to-end fusion events. In contrast, there was a further decline of telomere capping function in G3 iPSCs. In addition to telomere dysfunction, mitochondria function was severely impaired in G3 iPSCs as evidenced by oxygen consumption rate (OCR) decline, reactive oxygen species (ROS) accumulation and dramatically increased mitochondria genome mutations while these deficiencies were greatly mitigated in G3 ntESCs. Our data proved the principle that SCNT-mediated reprogramming appears more superior than transcription factors induced reprogramming in terms of the resetting of telomere quality and mitochondria function, and thus, providing valuable information for further improvement of transcription factors mediated reprogramming.
Publication Title
Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The mammary gland of the lactating mouse synthesizes and secretes milk lipid equivalent to its entire body weight in a single 20 day lactation cycle, making it one of the most active lipid synthetic organs known. To test the hypothesis that multiple metabolic control points and potential regulatory mechanisms are involved in activating lipid and lactose synthesis at the onset of lactation we compared the mammary transcriptome of 130 genes involved in glucose metabolism between late pregnancy and early lactation and in response to dietary fat. We utilized data obtained from microarray analysis of mammary glands from quadruplicate FVB mice at pregnancy day 17, and lactation day 2. Diets containing 8% or 40% lipid were fed from lactation days 5 to 10 and mammary glands and livers of triplicate FVB mice prepared for microarray analysis. We also compared the metabolome obtained from magnetic resonance spectroscopy of flash frozen glands of the mammary gland at day 17 of pregnancy with that at day 2 of lactation. The results provide a global picture of the multiple metabolic strategies utilized to turn a quiescent organ into an incredibly efficient machine for massive but balanced lipid and lactose synthesis and implicate the transcription factor SREBP-1c in regulation of part of the pathway.
Publication Title
Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 175 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objectives of this study were to measure effects of an aspirin intervention on gene expression in normal colonic epithelial and stromal tissue in healthy humans and to determine whether response differed by UGT1A6*2 genotype. We also sought to characterize gene expression differences within colonic tissue microenvironments by identifying genes that were differentially expressed between epithelial and stromal tissue.
Publication Title
Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs de novo lipogenesis.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples