Filters
Technology
Platform
GSE63898
Homo sapiens
396 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Genome-wide expression analysis of 228 hepatocellular carcinoma and 168 cirrhotic samples as part of a integrated study of gene expression and DNA-methylation de-regulation in patients with hepatocellular carcinoma
Publication Title
DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Mesenchymal stem cells (MSCs) And osteolineage cells contribute to the hematopoietic stem cell (HSC) Niche in the bone marrow of long bones. However, Their developmental relationships remain unclear. Here we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin- MSCs participate in fetal skeletogenesis, And lose MSC activity soon after birth. In contrast, Quiescent neural-crest-derived nestin+ Cells in the same bones preserve MSC activity, But do not generate fetal chondrocytes. Instead, They differentiate into HSC-niche-forming MSCs, Helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ PDGFR- Cell population also contains Schwann-cell precursors, But does not comprise mature Schwann cells. Thus, In the developing bone marrow HSC-niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, And ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation. Overall design: Total RNA was isolated from small numbers of FACS sorted stromal cells, obtained from neonatal Nes-Gfp bone marrow preparations (2 biological replicates). Each independent set of samples was obtained from pooled skeletal elements (long bones and sterna) form multiple littermates.
Publication Title
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Endocrine therapies targeting the proliferative effect of 17-estradiol (17E2) through estrogen receptor (ER) are the most effective systemic treatment of ER-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through a molecular mechanism that is not yet fully understood. The long-term estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors (AIs) in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ER. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were influenced by transcription factors known to be involved in acquired resistance or cell proliferation (e.g. IRF1 and E2F1, respectively) but, notably, not by canonical ER transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)- to pS167-ER were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ER-negative status, early response to letrozole and recurrence after tamoxifen treatment. This study proposes a mechanism for acquired resistance to estrogen deprivation that is coordinated across biological levels and independent of canonical ER function.
Publication Title
Biological reprogramming in acquired resistance to endocrine therapy of breast cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Estrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM Overall design: LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)
Publication Title
Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow (BM) microenvironment might contribute to the clinical outcomes of this common event. We previously showed that BM nestin+ mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin+ MSCs are consistently reduced in the BM of MPN patients and mice expressing the human JAK2V617F mutation in HSCs. Unexpectedly, MSC reduction is not due to differentiation but is caused by BM neural damage and Schwann cell death triggered by interleukin-1b produced by mutant HSCs. In turn, in vivo depletion of nestin+ cells or their production of CXCL12 expanded mutant HSCs and accelerated MPN progression. In contrast, administration of neuroprotective or sympathomimetic drugs prevented mutant HSC expansion. Treatment with b3-adrenergic agonists that restored the sympathetic regulation of nestin+ MSCs prevented the loss of these cells and blocked MPN progression by indirectly reducing leukaemic stem cells. Our results demonstrate that mutant HSC-driven niche damage critically contributes to disease manifestation in MPN and identify niche-forming MSCs and their neural regulation as promising therapeutic targets.
Publication Title
Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow (BM) microenvironment might contribute to the clinical outcomes of this common event. We previously showed that BM nestin+ mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin+ MSCs are consistently reduced in the BM of MPN patients and mice expressing the human JAK2V617F mutation in HSCs. Unexpectedly, MSC reduction is not due to differentiation but is caused by BM neural damage and Schwann cell death triggered by interleukin-1b produced by mutant HSCs. In turn, in vivo depletion of nestin+ cells or their production of CXCL12 expanded mutant HSCs and accelerated MPN progression. In contrast, administration of neuroprotective or sympathomimetic drugs prevented mutant HSC expansion. Treatment with b3-adrenergic agonists that restored the sympathetic regulation of nestin+ MSCs prevented the loss of these cells and blocked MPN progression by indirectly reducing leukaemic stem cells. Our results demonstrate that mutant HSC-driven niche damage critically contributes to disease manifestation in MPN and identify niche-forming MSCs and their neural regulation as promising therapeutic targets. Overall design: CD45- CD31- Ter119- GFP+ cells were sorted from the BM of Nes-gfp;Mx1-cre;JAK2-V617F mice and control littermates 6 weeks after pIpC treatment and were subjected to RNA sequencing. Each sample was pooled from 3 animals of the same genotype.
Publication Title
Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The Cytoplasmic Polyadenylation Element Binding (CPEB)-family of RNA-binding proteins regulates pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, the specific functions of each CPEB in the adult organism are poorly understood. Here we show that CPEB4 is required to suppress high fat diet- and aging-induced endoplasmic reticulum (ER) stress, and its subsequent hepatic steatosis. Stress-activated expression of CPEB4 in the liver is controlled through a double layer of regulation. First, Cpeb4 is transcriptionally regulated by the circadian clock and then, its mRNA translation is regulated by the Unfolded Protein Response (UPR) through the upstream Open Reading Frames (uORFs) present in its 5’ UTR. Thus, CPEB4 is synthesized only upon ER-stress but the amplitude of the induction is circadian. In turn, CPEB4 activates a second wave of UPR-translation required to maintain ER and mitochondrial homeostasis. Our results suggest that combined transcriptional and translational regulation of CPEB4 generates a “circadian mediator”, which?coordinates the hepatic UPR activity with periods of high ER protein-folding demand preventing non-alcoholic fatty liver disease (NAFLD). Overall design: mRNA profiles of total liver RNA and liver ER-associated RNA from WT and CPEB4-KO mice
Publication Title
Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples