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SRP178252
Mus musculus
2 Downloadable Samples
NextSeq 500
Description
R-spondin (Rspo) signaling is crucial for stem cell renewal and tissue homeostasis in the gastrointestinal tract. In the stomach, Rspo is secreted from myofibroblasts and controls epithelial gland regeneration by inducing proliferation of Wnt-responsive Axin2+ cells in the isthmus of the gland. Infection with H. pylori results in increased expression of stromal Rspo, leading to an expansion of Axin2+ isthmus stem cells and gland hyperplasia. Lgr5+ cells in the gland base are exposed to Rspo3 but the effects of this are not well understood. Here we demonstrate that apart from its activity as a mitogen, endogenous Rspo3 regulates gene expression of Lgr5+ cells in the gastric gland base. Surprisingly, Rspo3 induces differentiation within the Lgr5+ compartment towards secretory deep mucous cells. Moreover, the Rspo3-Lgr5 axis turns out to be a stimulus of epithelial antimicrobial defense. Infection with H. pylori induces a strong antimicrobial response, with Lgr5+ cells expressing antimicrobial compounds that are secreted into the lumen in an Rspo3-dependent manner. Depletion of Lgr5+ cells or knockout of Rspo3 in myofibroblasts leads to hyper-colonization of gastric glands, including the stem cell compartment, whereas systemic application of recombinant Rspo clears H. pylori from the glands. We provide an intriguing, unexpected feature of the Rspo3-Lgr5 axis in the stomach, exhibiting antimicrobial self-protection of the gland to protect the stem cell compartment from invading pathogens. Overall design: Lgr5eGFP reporter mice were infected with H. pylori for 2 months, uninfected mice served as controls. Mice were sacrificed and isolated, sorted Lgr5eGFP+ cells from the stomach antrum were used for single cell RNAseq using the 10x genome platform.
Publication Title
R-spondin-3 induces secretory, antimicrobial Lgr5<sup>+</sup> cells in the stomach.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
One of the most common genetic alterations in acute myeloid leukemia is the internal tandem duplication (ITD) in the FLT3 receptor for cytokine FLT3 ligand (FLT3L). The constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on normal hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. We report that young pre-leukemic mice with the Flt3ITD knock-in allele manifest an expansion of all DCs including classical (cDCs) and plasmacytoid (pDCs). The expansion originated in DC progenitors, occurred in a cell-intrinsic manner and was further enhanced in Flt3ITD/ITD mice. The mutation caused the downregulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T cells (Tregs). Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity in the absence of Tregs. Thus, the FLT3-ITD mutation directly affects DC development, thereby indirectly modulating T cell homeostasis and supporting Treg expansion. This effect of FLT3-ITD may subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. Overall design: Sorted splenic dendritic cell subsets from either Flt3+/+ or Flt3ITD/+ mice were sequenced for mRNA profiling. For each subset per genotype contains 2-3 replicates, all from independent experiments.
Publication Title
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HumanWG-6_V2_0_R2
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6_V2_0_R2
Description
We surveyed DNA methylation profiles of all human RefSeq promoters in relation to gene expression and differentiation in adipose tissue, bone marrow and muscle mesenchymal progenitors, as well as in bone marrow-derived hematopoietic progenitors. We unravel strongly overlapping DNA methylation profiles between adipose stem cells (ASCs), bone marrow mesenchymal stem cells (BMMSCs) and muscle progenitor cells (MPCs), while hematopoietic progenitor cells (HPCs) are more epigenetically distant from MSCs seen as a whole. Differentiation resolves a fraction of methylation patterns common to MSCs, generating epigenetic divergence.
Publication Title
Promoter DNA methylation patterns of differentiated cells are largely programmed at the progenitor stage.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The object of this study was to investigate the effect of elevated glucose concentrations (15 and 25 mM glucose) on gene expression in undifferentiated and adipogenic differentiated ASCs.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The aim of this study was to characterize basal gene expression for proliferating adipose tissue MSCs, cultured at normal cell culture conditions.
Publication Title
Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 135 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression data were generated on 136 subjects from the COPDGene study using Affymetrix microarrays. Multiple linear regression with adjustment for covariates (gender, age, body mass index, family history, smoking status, pack years) was used to identify candidate genes and Ingenuity Pathway Analysis was used to identify candidate pathways.
Publication Title
Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
All living cells rely on the communication with other cells to ensure their function and survival. Molecular signals are sent among cells of the same cell type and from cells of one cell type to another. In cancer, not only the cancer cells themselves are responsible for the malignancy, but also stromal (non-cancerous) cells and the molecular signals they send to cancer cells are important factors that determine the severity and outcome of the disease. Therefore, the identification of stromal signals and their influence on cancer cells is important when looking for novel treatment strategies.
Publication Title
Causal Modeling of Cancer-Stromal Communication Identifies PAPPA as a Novel Stroma-Secreted Factor Activating NFκB Signaling in Hepatocellular Carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 319 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Cancer-related fatigue is one of the most frequent complaints among breast cancer survivors, with a major negative impact on general life. However, the etiology behind this syndrome is still unraveled. Gene expression analysis was performed on whole blood samples from breast cancer survivors classified as either fatigued or non-fatigued at two consecutive time points. The analysis identified several gene sets concerning plasma and B cell pathways as different between the fatigue and non-fatigue groups, suggesting that a deregulation in these pathways might underlie the fatigue syndrome. The fatigue group also showed a higher mean level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigue group, thus further implicating the immune system in the biology behind the fatigue syndrome.
Publication Title
Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors.
Sample Metadata Fields
Specimen part, Subject
View Samples