Stat5a and Stat5b proteins are highly homologous with greater than 90% amino acid identity and share binding to the palindromic Stat5 consensus sequence, TTCNNNGAA, but individual roles of each transcription factor in breast cancer have not been thoroughly evaluated. To determine the degree of similarity between transcripts modulated by Stat5a and Stat5b proteins in human breast cancer, we utilized genome-wide transcript profiling to identify genes regulated specifically by Stat5a or Stat5b in response to prolactin.
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes.
Cell line
View SamplesResults of knocking-down AREG expression in SUM-149 cells by lenitviral infection of shRNA vectors and measuring gene expression provides information as to what genes are regulated by AERG in inflammatory breast cancer cells.
Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer.
Disease, Disease stage, Cell line
View SamplesEstrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
ERRα metabolic nuclear receptor controls growth of colon cancer cells.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Age, Specimen part
View SamplesTranscriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from young, and old mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Specimen part
View SamplesTranscriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from old, and post-mortem mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Age, Specimen part
View SamplesThe major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN- in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN- transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the measles virus-infected brain.
Age, Specimen part, Treatment
View SamplesThe three-dimensional (3D) folding of the chromosomal fibre in the human interphase nucleus is an important, but poorly understood aspect of gene regulation. Especially basic principles of 3D chromatin and chromosome organisation are still elusive. In this paper, we quantitatively analyse the 3D structure of large parts of chromosomes 1 and 11 in the G1 nucleus of human cells and relate it to the human transcriptome map (HTM). Despite a considerable cell-to-cell variation, our results show that subchromosomal domains, which are highly expressed, are more decondensed, have a more irregular shape and are located in the nuclear interior compared to clusters of low expressed genes. These aspects of chromosome structure are shared by six different cell lines and therefore are independent of cell type specific differences in gene expression within the investigated domains. Systematic measurements show that there is little to no intermingling of chromatin from different parts of the same chromosome, indicating that the chromosomal fibre itself is a compact structure. Together, our results reveal several basic aspects of 3D chromosome architecture, which are related to genome function.
The three-dimensional structure of human interphase chromosomes is related to the transcriptome map.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Specimen part, Disease
View SamplesPersistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) relates to inferior survival in multiple myeloma (MM). MRD PCs are therefore a minor clone able to recapitulate the initial tumor burden at relapse and accordingly, its characterization may represent a unique model to understand chemoresistance; unfortunately, the MRD clone has never been biologically investigated. Here, we compared the antigenic profile of MRD vs. diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study, and showed that the MRD clone is enriched by cells over-expressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4) and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs. diagnostic PCs showed identical copy number alterations (CNAs) in 3/8 cases, 2 patients with linear acquisition of additional CNAs in MRD clonal PCs, and 3 cases with variable acquisition and loss of CNAs over time. The MRD clone showed significant downregulation of genes particularly related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and identifies chemoresistant PCs in vitro. Together, we show that therapy-induced clonal selection is already present at the MRD stage, in which chemoresistant PCs show a specific phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles.
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Specimen part, Disease
View Samples