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SRP148659
Homo sapiens
671 Downloadable Samples
Illumina HiSeq 2500
Description
To define molecular markers of tyrosine kinase inhibitor-induced cardiotoxicity, we measured transcriptome changes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with one of four tyrosine kinase inhibitors (Erlotinib, Lapatinib, Sorafenib, or Sunitinib) displaying a range of mild to severe cardiotoxicity or a vehicle-only control (DMSO). Gene expression changes were assessed at the cell population level using total RNA-seq, which measured levels of both mRNAs and non-coding RNAs. hiPSC-CMs used in this study were the Cor.4U cells purchased from Ncardia. Overall design: hiPSC-CMs were treated with each TKI (Erlotinib, Lapatinib, Sorafenib or Sunitinib) at three doses (1, 3 and 10 µM) for 24 hours and the intermediate dose (3 µM) for an additional three time points (6h, 72h and 168h). hiPSC-CMs were also treated with the DMSO vehicle-only control at four time points (6h, 24h, 72h and 168h). Each treatment condition had three biological replicates, collected from three independent experiments using three different lots of hiPSC-CMs. Total RNA was collected from all these samples.
Publication Title
Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming.
Sample Metadata Fields
Sex, Specimen part, Subject, Compound, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.
Publication Title
Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The aim of the dataset was to study on a genome-wide level the impact of Lat deficiency on gene expression in resting and activated CD4+ T cells
Publication Title
Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
The mechanistic links between transcription factors and the epigenetic landscape, which coordinate the deregulation of gene networks during cell transformation are largely unknown. We used an isogenic model of stepwise tumorigenic transformation of human primary cells to monitor the progressive deregulation of gene networks upon immortalization and oncogene-induced transformation. By combining transcriptome and epigenome data for each step during transformation and by integrating transcription factor (TF) - target gene associations, we identified 142 Tfs and 24 chromatin remodelers/modifiers (CRMs), which are preferentially associated with specific co-expression paths that originate from deregulated gene programming during tumorigenesis. These Tfs are involved in the regulation of divers processes, including cell differentiation, immune response and establishment/modification of the epigenome. Unexpectedly, the analysis of chromatin state dynamics revealed patterns that distinguish groups of genes, which are not only co-regulated but also functionally related. Further decortication of TF targets enabled us to define potential key regulators of cell transformation, which are engaged in RNA metabolism and chromatin remodelling. Our study suggests a direct implication of CRMs in oncogene-induced tumorigenesis and identifies new CRMs involved in this process. This is the first comprehensive view of gene regulatory networks that are altered during the process of stepwise human cellular tumorigenesis in a virtually isogenic system.
Publication Title
Reconstruction of gene regulatory networks reveals chromatin remodelers and key transcription factors in tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Psoriasis is a chronic inflammatory skin disease of unknown etiology. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Topical application of Imiquimod, a Toll-like receptor 7 agonist, induces psoriasis in patients and psoriasiform inflammation in mice. We showed that daily application of Imiquimod for 14 days recapitulated both the initiation and the maintenance phase of psoriasis. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs and macrophages in the skin, we characterized their dynamics during both phases of psoriasis. During the initiation phase, neutrophils infiltrated the epidermis whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the maintenance phase, LCs and macrophage numbers increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by transcriptional analysis. Continuous depletion of LCs during the course of Imiquimod treatment aggravated chronic psoriatic symptoms as documented by an increased influx of neutrophils and a stronger inflammation. Therefore, by developing a mouse model that mimics the human disease more accurately, we established that LCs play a negative regulatory role during the maintenance phase of psoriasis.
Publication Title
Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have integrated dynamic RXRa binding, chromatin accessibility and promoter epigenetic status with the transcriptional activity inferred from RNA polymerase II mapping and transcription profiling. This demonstrated a temporal organization structure, in which early events are preferentially enriched for common GRNs, while cell fate specification is reflected by the activation of late programs in a cell-type specific manner. Furthermore, significant differences in cell lines' promoter status of genes associated with cell-line specific programs were inferred. Finally, a variety of transcription factors (TFs) playing a direct role in the signal transduction cascade downstream of the RXR/RAR initiated wiring were identified, several of them commonly regulated in both model systems, but in addition cell-type specific TF drivers were also identified.
Publication Title
Reconstructed cell fate-regulatory programs in stem cells reveal hierarchies and key factors of neurogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Plasmacytoid dendritic cells wre isolated from cutaneous lymph nodes of control C57BL/6 mice and used for microarray analysis.
Publication Title
Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Numerous CD11b+ myeloid cells are present within the dermis. They are very heterogeneous and can be divided in dermal DCs, tissue monocytes and tissue macrophages. At steady state, only CD11b+ DC migrate from the dermis to the skin draining lymph nodes whereas upon DNFB-induced inflammation, CD11b+ DC as well as dermal monocytes migrated to the lymph nodes. The objective of this study was to use gene expression profiling to rigorously identify the different subsets of dermal CD11b+ myeloid cells at steady state and upon inflammation and to characterize their functional potential.
Publication Title
Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples