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GSE33135
Homo sapiens
17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glucocorticoids are part of the therapeutic armamentarium of chronic lymphocytic leukemia where it has been suggested that cells with unmutated IGHV genes exhibit higher sensitivity. The mechanisms by which glucorticoids are active in CLL are not well elucidated.
Publication Title
Differential gene expression profile associated to apoptosis induced by dexamethasone in CLL cells according to IGHV/ZAP-70 status.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 134 Downloadable Samples
NextSeq 500
Description
Cellular function is strongly dependent on surrounding cells and environmental factors. Current technologies are limited in characterizing the spatial location and unique gene-programs of cells in less structured and dynamic niches. Here we developed a method (NICHE-seq) that combines photoactivatable fluorescent reporters, two-photon microscopy and single-cell RNA-seq to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and unique gene-programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the marginal zone. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways. Overall design: Transcriptional profiling of single cells from the specific immune niches in the lymph node and spleen, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500
Publication Title
Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 118 Downloadable Samples
- NextSeq 500
Description
In multicellular organisms, dedicated regulatory circuits control cell-type diversity and response. The crosstalk and redundancies within these circuits and substantial cellular heterogeneity pose a major research challenge. We present CRISP-seq, an integrated method for massively parallel single-cell RNA-seq and CRISPR pooled screens. We show that profiling the perturbation and transcriptome in the same cell, enables to elucidate, the function of multiple factors and their interactions. In this benchmarking study, we applied this technology to probe regulatory circuits of innate immunity. By sampling tens of thousands of perturbed cells in vitro and in mice, we identified interactions and redundancies between developmental and signaling-dependent factors controlling the commitment toward different cell lineages or the inflammatory and antiviral pathways. CRISP-seq thereby emerges as a broadly applicable, comprehensive, and unbiased approach for elucidating mammalian regulatory circuits. Overall design: Transcriptional and CRISPR profiles from single myeloid cells, infected with lentiviral vectors carrying different gRNAs, were generated by deep sequencing of tens of thousands of single cells, sequenced in several batches in an Illumina Nextseq 500. Experiment was paired-end, but read2 was used to read cell and molecule barcodes only. Additional details about experimental design (associating each single cell with its amplification batch and index sorting readout) available as Series supplementary file.
Publication Title
Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting.
Publication Title
Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 179 Downloadable Samples
- NextSeq 500
Description
Lung development and function arises from the interactions between diverse cell types and lineages. Using single cell RNA-seq we characterize the cellular composition of the lung during development and identify vast dynamics in both the composition of cells and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, ILC and basophils. Using IL33-receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and GM-CSF, characterized by unique signaling of cytokines and growth factors important for stromal, epithelial and myeloid cell fates. Antibody depletion strategies, diphtheria toxin–mediated selective depletion of basophils, and co-culture studies, show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole tissue cell interaction analysis on the single cell level can broaden our understanding of cellular networks in health and disease. Overall design: Transcriptional profiling of single cells from the different timepoints of lung development, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500 metadata.txt: Meta data file associating each single cell with its amplification batch and index sorting readouts
Publication Title
Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 80 Downloadable Samples
- NextSeq 500
Description
The immune system generates pathogen-tailored responses. The precise innate immune cell types and pathways that direct robust adaptive immune responses have not been fully characterized. By using fluorescent pathogens combined with massively parallel single cell RNA-seq, we comprehensively characterized the initial 48 hours of the innate immune response to diverse pathogens. We found that across all pathogens tested, most of the lymph node cell types and states showed little pathogen-specificity. In contrast, the rare antigen-positive cells displayed pathogen-specific transcriptional programs as early as 24 hours after immunization. In addition, mycobacteria activated a specific NK driven IFN? response. Depletion of NK cells and IFN? showed that IFN? initiated a monocyte specific signaling cascade, leading to production of major chemokines and cytokines that promote Th1 development. Our systems immunology approach sheds light on early events in innate immune responses and may help further development of safe and efficient vaccines. Overall design: Transcriptional profiling of single cells from pathogen-injected mouse auricular lymph nodes, generated from deep sequencing of thousands of cells, sequenced in several batches on illumina Nextseq500. For all experiments, innate immune lymph node cells were sorted accordng to the markers indicated in Samples' Characteristics "selection marker" field into 384-well MARS-seq2.0 cell capture plates. Sorting of antigen-carrying cells (Ag+) was based on the AF488-fluorescence of the pathogens injected. Different pathogens and time points were used, as indicated in the Samples' Characteristics "infection" and "time points" fields.
Publication Title
Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The vascular lining cells in the human spleens include littoral cells (LCs) and other splenic vascular endothelial cells (SVECs). LCs that comprise about 30 percent of the splenic red pulp are specialzed endothelial cells distinct from SVECs. They line the splenic sinusoids and function as the filters and scavengers for senescent or altered red blood cells. Patients with advanced forms of myelofibrosis (MF) often develope extramedullary hematopoiesis in the spleen.Vascular lining cells within MF spleens are thought to serve as a supportive microenvironment for MF hematopoietic cells. In this study we isolated MF and normal LCs and SVECs from human spleens using immunostaining and flow cytometric sorting and used microarrays to analyze the underling mechanism of LCs' unique functions that distinguish them from SVECs, and the properties of MF LCs and SVECs and their contributions to the microenvironment of MF spleens.
Publication Title
The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the hematopoietic microenvironment, endothelial cells (ECs) play an important role in the regulation of hematopoietic cell proliferation and trafficking. We previously demonstrated that EC stimulated with tumor necrosis factor alpha (TNF-) induce the generation of dendritic cells from CD34(+) stem cells, whereas in contrast, interleukins were capable of inducing the proliferation of hematopoietic and myeloid progenitors.
Publication Title
Transcriptional profiling of the hematopoietic support of interleukin-stimulated human umbilical vein endothelial cells (HUVECs).
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Follistatin is a folliculogenesis regulating protein that has been found in relatively high concentration in the female ovarian tissues. Follistatin acts as an antagonist to the function of Activin, which is often found elevated in ovarian carcinogenesis and thus presents a possibility for therapeutic intervention in controlling ovarian cancer. Most of the ovarian cancer occurs in its ovarian surface epithelium (OSE) cells. Although breast cancer susceptibility gene 1 (BRCA1) is a known tumor suppressor for breast cancer but its role in ovarian cancer is beginning to unfold. We have shown that in ovarian carcinoma cells (SKOV3), stable overexpression of BRCA1 stimulates Follistatin secretion and simultaneously downregulates Activin expression. Moreover, knock down of BRCA1 in immortalized OSE (IOSE) cells from human ovarian tissue demonstrates downregulation of Follistatin secretion with simultaneous up regulation of Activin expression. IOSE cells generated from an ovarian cancer patient with BRCA1 mutation failed to secrete Follistatin in the medium. Our results indicate a novel function for BRCA1 in the form of regulation of the expression of Follistatin in the ovarian cells.
Publication Title
BRCA1 regulates follistatin function in ovarian cancer and human ovarian surface epithelial cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Previous reports have shown low vitamin D serum levels and polymorphisms in the vitamin D receptor (VDR) to be associated with increased risk for TB. Given that 1,25-dihydroxyvitamin D3 has a role in lipid metabolism control, we tested whether the link between 1,25-dihydroxyvitamin D3 and tuberculosis involves macrophage lipid metabolism. Since formation of lipid droplets (LD) is a hallmark of lipid dysregulation in M. tuberculosis-infected macrophages, we measured LD content as a readout of altered lipid metabolism in infected THP-1 cells. Induction of LD, which peaked by 24 hours post-infection was prevented by addition of 1,25-dihydroxyvitamin D3 at the time of infection. To investigate the mechanism of 1,25-dihydroxyvitamin D3 modulation of LD formation, we analyzed the transcriptome of M. tuberculosis-infected THP-1 cells with and without 1,25-dihydroxyvitamin D3 treatment.
Publication Title
Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis infection.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples