This SuperSeries is composed of the SubSeries listed below.
Site-specific programming of the host epithelial transcriptome by the gut microbiota.
Sex, Specimen part
View SamplesThis study was conducted to determine heterogeneity of cancer-associated fibroblasts (CAFs) in mammary tumors, by unsupervised analysis of single cell transcriptomes. Overall design: 768 single EpCAM-, CD45-, CD31- NG2- fibroblasts were isolated from mammary tumors of two 14 week old MMTV-PyMT mice. The cells were sequenced following the Smart-Seq2 protocol (Picelli et al. Nature Methods 2013).
Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing.
Age, Specimen part, Cell line, Subject
View SamplesGlobal gene expression analysis was performed to investigate the changes of the fibroblast phenotype after four-week inductions toward adipocytic, osteoblastic and chondrocytic lineages. Human cells.
Interpreted gene expression of human dermal fibroblasts after adipo-, chondro- and osteogenic phenotype shifts.
Specimen part
View SamplesBackground: Arrhythmogenic cardiomyopathy (ACM) is a genetic autosomal disease characterized by abnormal cell-cell adhesion, cardiomyocyte death, progressive fibro-adipose replacement of the myocardium, arrhythmias and sudden death. Several different cell types contribute to the pathogenesis of ACM, including, as recently described, cardiac stromal cells (CStCs). In the present study, we aim to identify ACM-specific expression profiles of human CStCs derived from endomyocardial biopsies of ACM patients and healthy individuals employing TaqMan Low Density Arrays for miRNA expression profiling, and high throughput sequencing for gene expression quantification. Results: We identified 5 miRNAs and 272 genes as significantly differentially expressed. Both the differentially expressed genes as well as the target genes of the ACM-specific miRNAs were found to be enriched in cell adhesion related biological processes. Functional similarity and protein interaction based network analyses performed on the identified deregulated genes, miRNA targets and known ACM-causative genes revealed clusters of highly related genes involved in cell adhesion, extracellular matrix organization, lipid transport and ephrin receptor signaling. Conclusions: We determined for the first time the coding and non-coding transcriptome characteristic of ACM cardiac stromal cells, finding evidence for a potential contribution of miRNAs to ACM pathogenesis or phenotype maintenance. Besides known pathways, we identified also deregulation of genes encoding ephrin receptors and ephrins, thus suggesting a potential involvement of Eph-ephrin signaling in CStCs from ACM hearts. Overall design: Expression profiles of cardiac stromal cells from 3 ACM patients were compared against those of cardiac stromal cells from 3 healthy individuals.
The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in human cardiac stromal cells.
Sex, Disease, Subject
View SamplesIn adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal but not perigonadal adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide DNA binding and RNA expression analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health. Overall design: Identification of adipocyte BCL6-regulated genes
Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity.
Sex, Specimen part, Subject
View SamplesLong-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical grade tumor-redirected TSCM cells starting from nave precursors. CD8+CD62L+CD45RA+ nave T cells enriched by streptamer-based serial positive selection were activated by CD3/CD28 engagement in the presence of IL-7, IL-21 and the glycogen synthase-3 inhibitor TWS119, and genetically engineered to express a CD19-specific chimeric antigen receptor (CD19-CAR). These conditions allowed for the generation of CD19-CAR modified TSCM cells that were phenotypically, functionally and transcriptomically equivalent to their naturally occurring counterpart. Compared with T cell products currently under clinical investigation, CD19-CAR modified TSCM cells exhibit enhanced metabolic fitness, persistence and anti-tumor activity against systemic acute lymphoblastic leukemia xenografts. Based on these findings, we have initiated a phase 1 clinical study to evaluate the activity of CD19-CAR modified TSCM in patients with B-cell malignancies refractory to prior allogeneic hematopoietic stem cell transplantation.
Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies.
Subject
View SamplesWe generated knock-in mice expressing GFP under the control of the endogenous GIP (Glucose-dependent Insulinotropic Polypeptide) promoter that enable the isolation of a purified population of small intestine K cells. Using RNA-Seq, we comprehensively characterized the transcriptomes of GIP-GFP cells as well as the entire enteroendocrine lineage derived from Neurogenin3 (Ngn3)-expressing progenitors. Overall design: We interrogated the whole transcriptome of FACS-isolated small intestine GIPGFP cells using high-throughput mRNA sequencing. We also obtained the global gene expression patterns of the entire enteroendocrine cell lineage as well as the non-enteroendocrine cell population, comprising enterocytes, goblet cells and Paneth cells. To achieve this, small intestine epithelial cells from male mice resulting from the breeding of Neurogenin3 (Ngn3)-Cre mice with ROSA26-LoxP-STOP-LoxP-tomato indicator mice were isolated based on Tomato fluorescence and negative staining for CD45. Due to the small cell numbers, we constructed each of the three RNA-Seq libraries (GIPGFP, Ngn3TOMATO, and Ngn3-) using a pool of equal amounts of individual RNA samples without RNA amplification.
RNA-Seq analysis of enteroendocrine cells reveals a role for FABP5 in the control of GIP secretion.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Longitudinal study of recurrent metastatic melanoma cell lines underscores the individuality of cancer biology.
Specimen part, Disease, Subject
View SamplesThe lncRNA LOC100130476 (named as WAKMAR2) was found to be down-regulated in epidermal keratinocytes in human chronic non-healing wounds compared to normal acute wounds and the intact skin. However, its biological role in keratinocytes during wound repair has not been studied.
WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines.
Specimen part
View SamplesTime course of early development of peripheral nerve, from embryonic day 9.5 to postnatal day 0.
Efficient isolation and gene expression profiling of small numbers of neural crest stem cells and developing Schwann cells.
No sample metadata fields
View Samples