Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM) that govern the delicate balance between HSC quiescence, self-renewal, and differentiation. It has been suggested that quiescent HSCs localize adjacent to BM arteriole endothelial cells in a significant and non-random distribution. This data suggests that the arteriole BM vascular niche may be the primary HSC niche. Because the BM arteriole niche is composed of tightly-associated pericytes, including smooth muscle actin+, LepR+, Nestin+, NG2+, and nonmyelinating Schwann cells, we sought to begin to uncouple the arteriole BM EC niche by examining its capacity to support the maintenance and expansion of HSCs ex vivo and in vivo. We developed a method to isolate and culture BM arteriole endothelial cells in serum-/growth factor-free conditions, allowing for a non-biased approach to examining their instructive function. Utilizing our protocol, we demonstrate that BM endothelial cells, but not BM stromal cells, have the capacity to expand long-term repopulating, multi-lineage HSCs in lieu of complex serum and cytokine supplementation. In addition, transplantation of arteriole endothelial cells promoted rapid hematopoietic recovery and protected HSCs following an LD50 dose of myeloablative irradiation. These data demonstrate that arteriole-derived BM endothelial cells are endowed with the necessary signals to support the self-renewal and regenerative capacity of LT-HSCs and that transplantation of arteriole BM endothelial cells could be used as a therapeutic means to decrease pancytopenias associated with myeloablative treatments to treat a wide array of disease states. Overall design: Transcriptome sequencing of bone marrow endothelial cells and bone marrow stroma, in vitro and in vivo, with and without HSC co-culture.
Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
Specimen part, Disease, Subject
View SamplesEndothelial cells from nine steady state tissues and two regenerating tissues (bone marrow and liver) were intravitally labeld, isolated via flow sorting, and immediately processed for RNA extraction.
Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.
Sex, Specimen part, Treatment, Time
View SamplesDevelopmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. Overall design: Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
Specimen part, Subject
View SamplesThe global gene expression profiles of ventral prostates of wild type mice and p110 beta transgenic mice.
A constitutively activated form of the p110beta isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice.
Age, Specimen part, Disease, Disease stage
View SamplesCase story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining)
Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue.
Specimen part
View SamplesAffymetrix Mouse Gene 1.0 ST Array profiles were generated from acticular cartilage derived from CBA and Str/ort mice at three ages (8W, 18W, 40W), corresponding to stages prior to, at and late after natural osteoarthritis (OA) onset in OA-prone Str/ort mice.
Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis.
Age, Specimen part
View SamplesAtopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. The goal of this study was to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD.
Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis.
Specimen part, Disease
View SamplesTo try to identify the mechanism of STAT3s indirect action we have used a genomic approach to map the binding sites of STAT3 within the genome and also used RNA-seq technology to map the changes in RNA expression and transcript isoform abundance in response to IL-10. Overall design: Examination of transcriptome changes in peritoneal macrophages when treated with IL-10 for 4 hours. RNA was extracted and sequenced.
Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-inflammatory response in macrophages.
Sex, Specimen part, Cell line, Subject
View SamplesPurpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.
Sex, Disease, Disease stage, Subject, Time
View SamplesRNA-seq was used to look at the transcriptome changes and the early events of T cell receptor stimulation in CD4+ T cells Overall design: CD4+ T cells were stimulated with immobilised anti-CD3/CD28 antibodies for 4 hours and RNA was extracted and subjected to RNA-seq analysis.
Discovery and characterization of new transcripts from RNA-seq data in mouse CD4(+) T cells.
Sex, Specimen part, Cell line, Treatment, Subject
View Samples