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Mus musculus
12 Downloadable Samples
Illumina Genome Analyzer
Description
Objective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Overall design: Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.
Publication Title
Maternal high-fat diet and obesity compromise fetal hematopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Nlrp6-/- lamina propria Ly6C-hi monocytes in response to AOM/DSS have deficient TNF production, but increased production of other pro-inflammatory cytokines as compared to WT
Publication Title
NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury.
Sample Metadata Fields
Specimen part
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GSE2531- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In this experiment we compared total RNA from two commonly used choriocarcinoma cell lines, JEG3 and BeWo, to identify differentially expressed transcripts.
Publication Title
Microarray analysis of BeWo and JEG3 trophoblast cell lines: identification of differentially expressed transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.
Publication Title
Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
Publication Title
Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To describe normal cardiac and brain development during late first and early second trimester in human fetuses using microarray and pathways analysis and the creation of a corresponding normal database. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac and brain development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15(H2) and 16-18(H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cut-off to determine differential gene expression for individual genes. Test for enrichment to identify functional groups were carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR.
Publication Title
Metabolic gene profile in early human fetal heart development.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 217 Downloadable Samples
- Illumina HiSeq 2500
Description
A prevalent hypothesis for the cell-to-cell coordination of the phenomena of early development is that a defined mixture of different mRNA species at specific abundances in each cell determines fate and behavior. With this dataset we explore this hypothesis by quantifying the abundance of every mRNA species in every individual cell of the early C. elegans embryo, for which the exact life history and fate is precisely documented. Overall design: Embryos of the 1-, 2-, 4-, 8- and 16-cell stage were dissected into complete sets of single cells, and each cell from each set was sequenced individually using SMARTer technology. 5-9 replicates were generated for each stage. Most cell identities were unknown upon sequencing, but were deduced from by their transcriptomes post hoc.
Publication Title
A Transcriptional Lineage of the Early C. elegans Embryo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 27 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
Trastuzumab (Herceptinâ„¢), a humanized monoclonal antibody targeting the extracellular domain of human epidermal growth factor receptor-2 (HER2), is one of the most successful examples of targeted therapies for HER2-positive breast cancer. However, drug resistance remains daunting challenges. New combinatorial regimen of CDK4/6 inhibitors plus trastuzumab is currently under active clinical investigations. In this study, we seek to prospectively model the in vivo response to CDK4/6 inhibitor Palbociclib (Pal) plus trastuzumab (Ab) using transgenic Her2/Neu mouse model in parallel with the current clinical trial scenario. We performed single cell RNA-seqencing (Drop-seq) to profile and compare tumor cells and infiltrated immune cells derived from control, Ab+Pal sensitive/residual (APS) and resistant/progressive (APR) tumors. We revealed that although Ab+Pal treatment enhanced antigen processing, presentation and interferon signaling on tumor cells, a distinct immunosuppressive immature myeloid cells (IMCs) infiltrated in the resistant tumor microenvironment to promote resistant phenotype. Based on single cell gene set enrichment analysis (profiling) guided drug screening, we identified and evaluated a combinatorial immunotherapy regimen. We found that combinatorial immunotherapy with receptor tyrosine kinase inhibitor Cabozantinib and immune checkpoint blockades overcome Ab+Pal resistance by inhibiting IMCs and enhancing anti-tumor immunity. Moreover, our rationally designed sequential combinatorial regimens enabled durable response and sustained controlling of the emergence of acquired resistance, thus significantly improved outcomes of rapidly evolving Her2/Neu positive breast cancers. Our results implicate that single-cell RNA sequencing profiling guided combinatorial immunotherapy as a strategy to mitigate the emergence of resistance and to achieve long-term therapeutic benefit merits clinical translation. Overall design: Drop-seq of tumor cells and tumor infiltrating immune cells derived from FVB/N MMTV-neu202Mul mice with different treatment/phenotypes (sensitive and resistant tumors).
Publication Title
Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Expression of the MT1-MMP gene induces a significant upregulation of of oncogenes and tumorignenic genes in 184B5-MT1 cells.
Publication Title
Membrane type-1 matrix metalloproteinase confers aneuploidy and tumorigenicity on mammary epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 35 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed mRNA transcriptional profiling on Drosophila S3 cells after 4 hours treatment with novel lipid storage inhibitors belonging to three different chemotypes. Overall design: Profiling of RNA expression after treatment with three pairs of active/inactive compounds or DMSO as a control in triplicates and without treatment in the presence/absence of oleic acid in sextuplicate.
Publication Title
A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics.
Sample Metadata Fields
Cell line, Subject, Compound
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