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SRP056638
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. Overall design: PolyA RNA purification and subsequent high-throughput sequencing were performed on two independent B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus, and on two independent fibroblast clonal cell lines, derived from 129S1/Sv x CAST/EiJ F1 and immortalized with SV40.
Publication Title
Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of Allelic bias in clonal lymphoblastoid cells. Abstract: In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ~20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. Overall design: Poly A purified total RNA was used for library construction using a method described by Parkhomchuk et. al. NAR 2009. The library was strand-specific but the pipeline for data analysis does not assume the library is strand-specific.
Publication Title
Chromatin signature of widespread monoallelic expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- NextSeq 500
Description
In this manuscript, we described male-biased mutations in chrX genes in cancer. In this RNA-seq experiment we tested the transcriptional consequences of shRNA knockdown of one of those genes, CNKSR2 Overall design: Murine NIH 3T3 cells were infected with and selected for expression of lentiviruses expressing shRNAs targeting Cnksr2 (2 independent shRNA sequences) or a control shRNA (targeting RFP, a gene not present in these cells). Each was performed in biological triplicate independent cultures for n=9 total samples
Publication Title
Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared human female hiPSC lines (all derived from IMR-90 fibroblasts) that were XIST RNA-positive and XIST RNA-negative. We also examined the gene expression patterns for 2 female hIPSCs (derived from different disease model fibroblasts) that were also negative for XIST RNA. hiPS 12D-1 is derived from Huntington's Disease patient and 6C-1 is derived from a Type I Diabetes Mellitus patient (Park et al Nature 2008).
Publication Title
Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- NextSeq500
Description
Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and it is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells is sufficient to induce luminal-to-basal phenotypic switch implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells. Overall design: RNA-Seq in breast cancer cell-lines
Publication Title
Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bmi1 is an important stem cell regulator in multiple tissues, including the lung.
Publication Title
Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. Overall design: mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21
Publication Title
Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCC) when compared to non metastasizing cSCC (non MSCC). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NFB signaling pathway. Accordingly, non MSCC display higher levels of membranous pS176 IKK and their stroma is enriched in neutrophils and eosinophils when compared to MSCC. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb depleted cSCC cells. Altogether these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high risk cSCC could benefit from clinical therapies addressed to harness the immune response.
Publication Title
The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Developing osteoblasts undergo a sequence of three consecutive phases: cell proliferation, extracellular matrix maturation, and mineralization. We investigated pH effects on these phases using the osteoblast-like cell line MC3T3-E1.
Publication Title
MC3T3 osteoblast-like cells cultured at alkaline pH: Microarray data (Affymetrix GeneChip Mouse 2.0 ST).
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation.
Publication Title
Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples