Filters
Technology
Platform
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD4 T cells are essential mediators of the asthmatic process. We used the clinically relevant allergen house dust mites to induce signs of allergy in mice and performed gene expression arrays specifically on CD4 T cells infiltrating the lung
Publication Title
Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 1120 Downloadable Samples
Illumina HiSeq 2000
Description
Naïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation. Overall design: Mice were sentized and challanged with HDM extract intranasally. scRNA-Seq was performed in 384-well format. The relevant organs (either BAL, lung or mLN) were isolated, rapidly processed, stained for a panel of surface markers and single cell sorted within approximately 90 minutes of organ harvest. In total 764 memory T helper cells (CD3+CD4+CD44+) were sorted directly into lysis buffer using a BD Influx from two independent mice 15 days after sensitization and challenge with HDM as described above. In addition, 50 naïve T Helper cells (CD3+CD4+CD62LhiCD44lo), 50 Treg cells (CD3+CD4+CD25hi) from mLN of a mouse not exposed to HDM; 200 ST2+ mLN and 82 ST2+ lung T helper cells (CD3+CD4+CD44+ST2+CD25-) were sort purified at day 10 of the HDM model. SMART-Seq2 libraries were prepared using the method described in Picelli et al. (Nature Methods 2013) by the Eukaryotic Single Cell Genomics national facility at SciLife Laboratory, Stockholm.
Publication Title
Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression. Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression.
Publication Title
The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
comparative expression between stromal MS5 cells treated with (MS5_PD18) or without (MS5_DMSO) MEKi
Publication Title
Interleukin-18 produced by bone marrow-derived stromal cells supports T-cell acute leukaemia progression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation.
Publication Title
RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used IMR90 ER:RAS cells infected with an empty vector or an shRNA for ARID1B and induced senescence by addition of 4OHT. 6 days later RNA was collected for gene expression analysis. With a functional screen we previously identified ARID1B as a new regulator of cellular senescence. By performing gene expression analysis we confirmed this finding and showed that knockdown of ARID1B prevents the expression of genes induced during senescence.
Publication Title
SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We discovered that the maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and IFN-? induced CD274 expression across different human and mouse tumor cell lines and primary patient samples. Mechanistically, BETi decreased Brd4 occupancy at the Cd274 locus without any change in Myc occupancy, resulting in transcriptional pausing and rapid loss of Cd274 mRNA production. Finally, targeted inhibition of the PD1/PD-L1 axis by combining anti-PD1 antibodies and the BETi JQ1 caused synergistic responses in mice bearing Myc-driven lymphomas. Our data uncovers a novel interaction between BETi and the PD-1/PD-L1 immune-checkpoint and provides novel insight into the transcriptional regulation of CD274. Overall design: RNA Sequencing of Eµ-Myc lymphoma cell lines treated for 2 hours with JQ1, or DMSO vehicle.
Publication Title
BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples
SRP110058- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
First, transcriptome analysis of purified CD31+ endothelial cells (ECs) from VEGF-treated sprouting embryoid bodies showed angiogenesis as the top affected category when Apelin is not present. In addition, loss of Apelin resulted in the modulation of pathways in ECs related to vasculogenesis, cell adhesion and response to hypoxia. Ingenuity Pathway Analysis (IPA) further identified VEGFR pathway as the main upstream regulator affected in endothelial cells, closely followed by the TGFß1 and TNF pathways, all reduced in the absence of Apelin. The most inhibited genes from the VEGFR pathway in the absence of Apelin are angiogenesis-related genes. Second, transcriptome analysis of CD31+/CD105+ ECs sorted from Apelin wild-type and Apln-depleted tumors found a significant decrease in processes associated with endothelial cell proliferation and angiogenesis in ECs sorted out of Apelin-depleted tumors using IPA. Further, IPA predicted a decrease in the adhesion of granulocytes and upstream regulator analysis showed that proteins of the TGF-superfamily, Inhibin-ßA and TGF-ß1, as well as C/EBP-alpha, ß-Catenin, ErbB2 and EGFR are predicted to be inhibited upstream regulators in ECs isolated from Apelin-depleted tumors. Overall design: Transcriptome analysis of purified CD31+ endothelial cells from VEGF-treated in vitro sprouting vessels in Apelin presence or absence. Transcriptome analysis of tumor endothelial cells from Apelin wild-type and depleted conditions. We report the application of Smart-Seq2 sequencing to populations of 100 endothelial cells, sorted from tumors that were Apelin wild-type or depleted.
Publication Title
Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Regulation of homeostasis and development of cardiac muscle tissues is controlled by a core set of transcription factors. The MEF2 family plays a critical role in these processes.
Publication Title
Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
Sample Metadata Fields
Specimen part, Disease
View Samples