Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune mediated destruction of ß cells. How ß cells respond to immune attack is unknown. We identified a population of ß cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal ß cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of ß cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclosphosphamide. Human ß cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long term survival of ß cells in some patients. Overall design: mRNA profiles of top and bottom beta cells were generated by RNA-seq. 4 samples were processed from each population of cells.
β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice.
Specimen part, Cell line, Subject
View SamplesHigh throughput sequencing of poly-A RNA Overall design: Two-condition experiment: Control- and Chronophin shRNA (CIN/PDXP) in glioblastoma stem-like cells
Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions.
Disease, Cell line, Subject
View SamplesWhilst the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognized, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. We have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. Whilst loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. We investigated whether there were common gene expression changes between EBV-positive and loss clones derived for four endemic Burkitt lyphoma cell lines that could explain the apoptosis sensitivity of clones that had lost EBV.
Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.
Cell line
View SamplesTumor associated macrophages show signs of both, classical pro-inflammatory as well as alternative macrophage activation. The aim of this study was to compare TAMs across tumor types, to characterize their phenotype in detail and to identify the signaling nodules involved regulating classical and alternative activation traits.
Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways.
Specimen part
View SamplesIn chronic lymphocytic leukemia (CLL), 13q14 and 11q22-23 deletions are found in 2/3 of the cases. 11q22-23 deletions are associated with poor survival, whereas 13q14 deletions as single abnormality are often found in indolent disease forms. The molecular basis for this difference in prognosis is not known.
Expression analysis of genes located in the minimally deleted regions of 13q14 and 11q22-23 in chronic lymphocytic leukemia-unexpected expression pattern of the RHO GTPase activator ARHGAP20.
Specimen part, Disease, Disease stage
View SamplesNatural killer T (NKT) cells identified by CD1d-tetramer and TCRb were isolated from the thymi of wild type and Ezh2 knockout mice. The NKT cells were FACS sorted into different stages based on the surface expression of CD44 and NK1.1. Overall design: For both wildtype and knockout mice, RNA was extracted from two biological replicates of CD44+ NK1.1- cells, one replicate of CD44+ NK1.1+ cells and one replicate of CD44- NK1.1- cells. Each RNA sample was divided into four and sequenced on four lanes of an Illumina HiSeq sequencer.
A non-canonical function of Ezh2 preserves immune homeostasis.
Specimen part, Subject
View SamplesLong-lived quiescent mammary stem cells (MaSCs) are presumed to coordinate the dramatic expansion of ductal epithelium that occurs through the different phases of postnatal development, but little is known about the molecular regulators that underpin the activation of MaSCs. Here we show that ablation of the transcription factor Foxp1 in the mammary gland profoundly impairs ductal morphogenesis, resulting in a rudimentary tree throughout adult life. Foxp1-deficient glands were highly enriched for quiescent Tspan8hi MaSCs, which failed to become activated, even in competitive transplantation assays, and therefore harbor a cell-intrinsic defect. Luminal cells aberrantly expressed basal genes, suggesting that Foxp1 may also contribute to cell-fate decisions. Notably, Foxp1 was uncovered as a direct repressor of the Tspan8 gene in basal cells and deletion of Tspan8 could rescue the profound defects in ductal morphogenesis elicited by Foxp1 loss. Thus, a single transcriptional regulator, Foxp1, can control the exit of MaSCs from dormancy to orchestrate differentiation and development. Overall design: Basal and luminal epithelial cells were extracted from the mammary glands of floxed Foxp1 control and Foxp1 mammary gland conditional knockout mice. mRNA from three biological replicates of each cell population was profiled by RNA sequencing. All mice were female.
Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence.
Specimen part, Cell line, Subject
View SamplesPreeclampsia complicates more than 3% of all pregnancies in the United States and Europe. High-risk populations include women with diabetes, dyslipidemia, thrombotic disorders, hyperhomocysteinemia, hypertension, renal diseases, previous preeclampsia, twin pregnancies, and low socioeconomic status. In the latter case, the incidence may increase to 20% to 25%. Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Preeclampsia is defined by systolic blood pressure of more than 140 mm Hg and diastolic blood pressure of more than 90 mm Hg after 20 weeks gestation in a previously normotensive patient, and new-onset proteinuria. Abnormal placentation associated with shallow trophoblast invasion (fetal cells from outer cell layer of the blastocyst) into endometrium (decidua) and improper spiral artery remodeling in the decidua are initial pathological steps.
Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.
No sample metadata fields
View SamplesIL17-producing ?d T cells (?d T17) mainly develop in the prenatal phase and persist as long-living self-renewing effector cell in all kind of tissues. They express polyclonal T-cell receptors (TCR), comprising public V?4+ and V?6+ TCRs with germline-like rearrangements. In particular, V?6+ T cells have recently been found in a variety of tissues including enthesis, gingiva or skin. However, their exchange between tissues and the mechanisms of tissue-specific adaptation and residency remain poorly understood. Here, we profiled V?6+ T cells isolated from thymus, peripheral lymph nodes (pLN) and skin through single-cell RNA-seq technology and compared those to V?4+ T cells. Our data demonstrated that V?6+ T cells formed highly homogenous cell populations that could be separated by tissue-specific gene expression signatures. Overall design: Sort V?4 and V?6 ?dT cells from peripheral lymph nodes, ear skin and thymus, then do 3'-RNA single cell sequencing (10x genomics).
Single-Cell Transcriptomics Identifies the Adaptation of Scart1<sup>+</sup> Vγ6<sup>+</sup> T Cells to Skin Residency as Activated Effector Cells.
Age, Specimen part, Cell line, Subject
View SamplesWe analysed the transcriptome of different HSC-enriched subpopulations of cells sorted from human umbilical cord blood and isolated from several individuals with different genetic backgrounds. We aim at identifying new cell surface markers associated with human HSC and downstream mature hematopoietic cell activity. Overall design: RNA-seq of CD34+CD45RA- cord blood cells from 17 non-pooled individuals.
GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.
Specimen part, Subject
View Samples