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GSE11681
Homo sapiens
37 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from patients with calpainopathy in which molecular diagnosis was ascertained were invest
Publication Title
Gene expression profiling in limb-girdle muscular dystrophy 2A.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transciptome analysis of CD34+ enriched human HSPC lentivirally transduced with cohesin WT or mutant
Publication Title
Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
Illumina HiSeq 4000
Description
Understanding the contribution of abnormal genetic and epigenetic programs to acute myeloid leukemia (AML) is necessary for the integrated design of targeted therapies. To investigate this, we determined the effect of epigenetic reprogramming on leukemic behavior by generating induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements. AML-derived iPSCs (AML-iPSCs) retained leukemic mutations, but reset leukemic DNA methylation/gene expression patterns and lacked leukemic potential. However, when differentiated into hematopoietic cells, AML-iPSCs reacquired the ability to give rise to leukemia in vivo and reestablished leukemic methylation/gene expression patterns, including an aberrant MLL signature, indicating that epigenetic reprogramming was insufficient to eliminate leukemic behavior. In one case, we identified distinct AML-iPSC KRAS mutant and wildtype subclones that demonstrated differential growth properties and therapeutic susceptibilities, predicting KRAS wildtype clonal relapse due to increased cytarabine resistance. Increased cytarabine resistance was further observed in a cohort of KRAS wildtype MLL-rearranged AML samples, demonstrating the utility of AML-iPSCs in predicting subclonal relapse and facilitating clonal targeting in AML. Overall design: RNA seq profiling of normal and leukemic differentiated and iPSC populations
Publication Title
Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells. We studied in vivo responses of normal and CTLA-4-deficient antigen-specific murine effector CD4+ T cells. In order to do these studies in a physiological model of immunity to foreign antigen, we transferred small numbers of congenically marked RAG2-deficient 5C.C7 T cells with either a normal or knockout allele of CTLA-4 into normal syngeneic B10.A recipient mice. The T cells were then activated by immunization with MCC peptide and LPS. To look for transcriptional signatures of negative regulation of T cell responses by CTLA-4, we used microarray analysis to compare transcripts in wild type and CTLA-4 KO 5C.C7 T cells four days after immunization. This is the first instance in which differences are observed in extent of accumulation of wild type and CTLA-4 KO 5C.C7 T cells.
Publication Title
Cutting edge: CTLA-4 on effector T cells inhibits in trans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 4000
Description
A LHX4 transgenic reporter line with high specificity for developing mouse cone photoreceptors was identified and used to purify early stage cone photoreceptors for profiling by single cell RNA sequencing. Overall design: Collection of FACS-sorted LHX4::GFP+ E14.5 early cones and LHX4::GFP- retinal cells for further analysis.
Publication Title
Identification of Genes With Enriched Expression in Early Developing Mouse Cone Photoreceptors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Gallus gallus
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
Marek’s disease virus 1 (MDV-1), an oncogenic -herpesvirus that induces T-cell lymphomas in chickens, serves as model system to study transformation by lymphotropic herpesviruses. Like the oncogenic human -herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), MDV-1 encodes several viral microRNAs (miRNAs). One MDV-1 miRNA, miR-M4, shares the same “seed” targeting sequence with both a KSHV miRNA, miR-K11, and cellular miR-155. Importantly, miR-M4 plays a critical role in T-cell transformation by MDV-1, while miR-K11 and cellular miR-155 are thought to play key roles in B-cell transformation by KSHV and EBV, respectively. Here, we present an analysis of the mRNAs targeted by viral miRNAs expressed in the chicken T-cell line MSB1, which is naturally coinfected with MDV-1 and the related nonpathogenic virus MDV-2. Our analysis identified>1,000 endogenous mRNAs targeted by miRNAs encoded by each virus, many of which are targeted by both MDV-1 and MDV-2 miRNAs. We present a functional analysis of an MDV-1 gene, RLORF8, targeted by four MDV-1 miRNAs and a cellular gene, encoding interleukin-18 (IL-18) and targeted by both MDV-1 and MDV-2 miRNAs, and show that ectopic expression of either protein in a form resistant to miRNA inhibition results in inhibition of cell proliferation. Finally, we present a restricted list of 9 genes targeted by not only MDV-1 miR-M4 but also KSHV miR-K11 and human miR-155. Given the critical role played by miR-155 seed family members in lymphomagenesis in humans and chickens, these mRNA targets may contain genes whose inhibition plays a conserved role in herpesvirus transformation. Overall design: PAR-CLIP experiment of MSB1 cells
Publication Title
Analysis of the mRNA targetome of microRNAs expressed by Marek's disease virus.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of knockdown of SDHD with or without knockdown of CDKN1C or SLC22A18 at gene expression level.
Publication Title
Parent-of-origin tumourigenesis is mediated by an essential imprinted modifier in SDHD-linked paragangliomas: SLC22A18 and CDKN1C are candidate tumour modifiers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.
Publication Title
Gefitinib induces myeloid differentiation of acute myeloid leukemia.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Various mesenchymal cell types have been identified as critical components of the hematopoietic stem/progenitor cell (HSPC) niche. Although several groups have described the generation of mesenchyme from human pluripotent stem cells (hPSC), the capacity of such cells to support hematopoiesis has not been reported. Here we have demonstrated that distinct mesenchymal subpopulations co-emerge from mesoderm during hPSC differentiation. Despite co-expression of common mesenchymal markers (CD73, CD105, CD90, PDGFRß), a subset of cells defined as CD146++CD140alow supported functional HSPC ex vivo while CD146-CD140a+ cells drove differentiation. The CD146++ subset expressed genes associated with the HSPC niche and high levels of the Wnt inhibitors. HSPC support was contact-dependent and was mediated in part through JAG1 expression. Molecular profiling revealed remarkable transcriptional similarity between hPSC-derived CD146++ and primary human CD146++ perivascular cells. The derivation of diverse pools of mesenchymal populations from hPSC opens potential avenues to model their developmental and functional differences and to improve cell-based therapeutics from hPSC. Overall design: Our goal was to analyze and compare transcriptome of human pluripoten stem cell-derived mesenchyme (CD146++ and CD146-) with primary human lipoaspirate tissue-derived pericyte (CD146+) and CD146- mesenchymal populations.
Publication Title
Transcriptionally and Functionally Distinct Mesenchymal Subpopulations Are Generated from Human Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples