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GSE54582
Mus musculus
222 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Publication Title
Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 68 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Assessment of mRNA expression levels in fat biopsies from subcutaneous adipose tissue from unrelated individuals.
Publication Title
A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Overexpression of USF1 in HEK293T cells in vitro to ascertain the genes downstream of USF1. Will identify direct targets as well as indirect targets of USF1.
Publication Title
A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hair Follicle regeneration relies on both epithelial components (bulge and hair germ cells) and a mesenchymal one (dermal papilla cells).
Publication Title
A two-step mechanism for stem cell activation during hair regeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Standardization of MSC manufacturing is urgently needed to facilitate comparison of clinical trial results. Here, we compare gene expression of MSC generated by the adaptation of a proprietary method for isolation and cultivation of a specific umbilical cord tissue-derived population of Mesenchymal Stromal Cells (MSCs)
Publication Title
Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from mESC and AntNPC for the following lines: WT mESC, WT AntNPC, EED-/- mESC and EED-/- AntNPC
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from AntNPC derived from mESC: WT AntNPC (four biological replicates), PE Lhx5(-109)-/- Clon1 AntNPC (two biological replicates) and PE Lhx5(-109)-/- Clon2 AntNPC (two biological replicates).
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 106 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
We analyzed total leukocyte gene expression using Affymetrix microarrays from healthy smokers, COPD patients and non-smoking control subjects before and after exposure to acute cigarette smoke (smoking two cigarettes in 30 minutes).
Publication Title
Systemic inflammatory response to smoking in chronic obstructive pulmonary disease: evidence of a gender effect.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Although Human papillomavirus infection is the main causal factor for cervical cancer (CC), there is data suggesting genetic factors could modulate the risk and progression of CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to cervical cancer, HPV infection and HPV types, a case-control study was performed in the Mexican mestizo population. The polymorphism of mtDNA D-Loop was investigated in 187 cervical cancer patients and 270 healthy controls. D-loop was amplified from a blood DNA sample and analyzed by sequencing. HPV was detected and typed in cervical scrapes from both groups. mtDNA polymorphisms were compared in the whole samples and stratified by HPV types. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (OR=1.6, 95% CI: 1.05-2.58) and showed an additive effect of 36% over the risk conferred by the HPV (OR=153, 95% CI: 65.4-357.5). The frequency of HPV 16, 18, 31 and 45 in cancer samples was similar in all haplogroups but one (D1). It showed a very low frequency of HPV16, any HPV18 and high frequency of HPVs 31, 45 and other types. Two mtDNA genes (MT-TD, MTTK) could be involved in the increased risk conferred by the haplogroup B2, since they were up-regulated exclusively in B2 tumors (p<0.05, t-test). These findings will contribute to clarify the importance of genetic factors in CC.
Publication Title
The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Gene expression in eukaryotes is an essential process that includes transcription, pre-RNA processing and RNA export. All these steps are coupled and normally, any failure in one step affects the other steps and could cause nuclear mRNA retention. One important player in this interface is the poly(A)-RNA binding protein Nab2, which regulates the poly(A)-tail length of mRNAs protecting their 3-ends from a second round of polyadenylation and facilitating their nucleo-cytoplasmic export. Interestingly, here we show that Nab2 has additional roles in mRNA transcription elongation, tRNA metabolism and rRNA export.
Publication Title
Nab2 functions in the metabolism of RNA driven by polymerases II and III.
Sample Metadata Fields
No sample metadata fields
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