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SRP066623
Homo sapiens
8 Downloadable Samples
IlluminaHiSeq2500
Description
One critical task in pluripotent reprogramming is to erase the somatic transcriptional program of starting cells. No strategy or theory exists for achieving erasure of somatic gene expression memory. Here, we present a proof-of-principle strategy in which reprogramming to pluripotency is facilitated by small molecules that erase somatic cell transcription memory. We show that mild chemical targeting of the acetyllysine-binding pockets of the BET bromodomains, the transcriptional bookmarking domains, robustly enhances reprogramming. Furthermore, we show that chemical targeting of the transcriptional bookmarking BET bromodomains dramatically downregulates specific somatic gene expression programs in both naïve and reprogramming fibroblasts. Chemical blocking of the BET bromodomains also resulted in loss of fibroblast morphology early in reprograming. In this study, we experimentally demonstrate a concept for cell fate conversion: facilitating the conversion by chemically targeting the transcriptional bookmarking BET bromodomains responsible for transcriptional memory. Overall design: human BJ cells were treated with JQ1 at 50 nM for 48 hours. Differential expression was compared with DMSO treatment. The same treatments and comparsion were conducted for reprogramming BJ cells, which were transduced with OCT4, SOX2, and KLF4. JQ1iPSC5 is a iPSC (induced pluripotent stem cell) line generated in this study using small molecules JQ1.
Publication Title
Reprogramming by De-bookmarking the Somatic Transcriptional Program through Targeting of BET Bromodomains.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.
Publication Title
MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hijacking a key chromatin modulator creates epigenetic vulnerability for MYC-driven cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
It remains unclear how epigenetic modulators impact the tumorigenic potential of Myc. Here we show that the core subunits, including Dpy30, of the major H3K4 methyltransferase complexes are selectively upregulated in Burkitt lymphoma, and Dpy30 is important for efficient genomic binding of Myc. Dpy30 heterozygosity does not affect normal animal physiology, but significantly suppressed lymphomagenesis and reduced expression of a subset of key pro-survival genes when Myc is hyper-activated. Dpy30 heterozygosity also impedes cellular transformation without affecting normal cell growth. These results suggest that Myc hijacks this chromatin modulator to coordinate its oncogenic program for efficient tumorigenesis, meanwhile creating epigenetic vulnerability, which we then exploited by specifically targeting Dpy30s activity to inhibit growth of the Burkitt lymphoma cell model.
Publication Title
Hijacking a key chromatin modulator creates epigenetic vulnerability for MYC-driven cancer.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
We isolated and characterized mouse neural stem cells that are heterozygous or null for Dgcr8 from E13.5 embryonic brain; Overall design: Examination transcriptional profiles of mouse neural stem cells heterozyous or null for Dgcr8
Publication Title
Canonical microRNAs Enable Differentiation, Protect Against DNA Damage, and Promote Cholesterol Biosynthesis in Neural Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Reduced or absent cytotrophoblast invasion of the maternal uterine spiral arteries is a common clinical finding in studies of pregnancies complicated by preeclampsia, suggesting that the mechanisms behind invasion of these cells is perturbed. The placenta initially develops in a low oxygen environment of 1-2% oxygen until after the 10th week of pregnancy. During this time oxygen concentration exerts a major influence over trophoblast activity and, in vitro, hypoxia inducible factors are proposed to be one of many key regulators of first trimester trophoblast behaviour. We used a global gene expression microarray approach to identify signalling pathways involved in invasion of the first trimester trophoblast cell line HTR8/SVneo under hypoxic conditions where HIF-1 was active. Additionally, first trimester placental samples from different gestational age groups were labelled with anti HIF-1 and HIF-2 to evaluate whether HIFs are differentially expressed and localised across the period of development characterised by hypoxia (6-8 weeks) and maternal blood perfusion (10-12 weeks). Eighty-eight genes were differentially expressed between cells cultured in 1% oxygen (where HIF-1 was localised to the nucleus) and 5% oxygen (where HIF-1 was cytoplasmic). 65% of the genes were predicted to contain HIF-1:ARNT transcription factor binding sites. Increased nuclear localisation of HIF-1 was seen in extravillous cytotrophoblasts in early first trimester compared with late, while cellular expression of HIF-2 in the villous stroma was higher in late first trimester. While HIFs and their downstream targets are clearly induced in trophoblasts during early placental development, and in vitro hypoxic conditions, the mechanism and pathways by which invasion is increased under hypoxic conditions is not clear from the gene expression profile. Further insight beyond the transcription level is required to fully understand this complex phenomenon.
Publication Title
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.
Sample Metadata Fields
Cell line, Treatment
View Samples