We hypothesized that tissue genome-wide gene expression analysis, coupled with gene network analyses of differentially expressed genes, would provide novel insights into the pathogenesis of pulmonary sarcoidosis.
Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.
Specimen part, Disease, Disease stage
View SamplesUsing wild-type and Rps5 heterozygous embryonic stem cells, we isolated RNA from polyribosomal fractions in order to get insights into transcriptional and translational defects of such deletion. Overall design: Input, monosomes and polysomes extracted RNA samples from wild-type and Rps5 heterozygous clones (undifferentiated and differentiated, total number of samples = 12), were subjected to sequencing.
Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View SamplesMyocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF.
Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.
Specimen part
View Samples3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting (FACS) at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005) and Molyneaux, BJ et al (2009). The hybridization cocktails used here were originally applied to the Affymetrix mouse 430A arrays and submitted as GEO accession number GSE2039. The same hybridization cocktails were then applied to the Affymetrix mouse 430 2.0 arrays, and those data are contained in this series.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View SamplesKey regulators of septum formation between the left and right ventricle in mammals, including the transcription factors TXB5 and PITX2, feature loss-of-function phenotypes that affect development of the two-chambered zebrafish heart, suggesting
Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.
Specimen part
View SamplesCultured pluripotent stem cells are a cornerstone of regenerative medicine due to their ability to give rise to all cell types of the body. While pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a very transient state in vivo, lasting 2-3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavorable conditions. Diapause is a strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that inhibition of mechanistic target of rapamycin (mTor), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent to give rise to embryonic stem (ES) cells and mice. We show that both natural diapause blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTor activity, translation and transcription. In addition, pausing can be induced directly in cultured ES cells and sustained for weeks in the absence of cell death or deviations from cell cycle distributions. We show that paused ES cells remain pluripotent, display a remarkable global suppression of transcription, and maintain a gene expression signature of diapaused blastocysts. These results allow for the first time the sustained suspension of development of a mammalian embryo in the laboratory, and shed light on the regulation of diapause and the origins of ES cells. Our findings have important implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and aging. Overall design: Examination of RNA expression profiles of embryonic stem cells in serum, 2i and paused states by RNA-seq
Inhibition of mTOR induces a paused pluripotent state.
Specimen part, Cell line, Treatment, Subject
View SamplesCell purification technology combined with whole transcriptome sequencing and small molecule agonist of hematopoietic stem cell self-renewal has allowed us to identify the endothelial protein c receptor protein (EPCR) as a surface maker that defines a rare subpopulation of human cells which is highly enriched for stem cell activity in vivo. EPCR-positive cells exhibit a robust multi-lineage differentiation potential and serial reconstitution in immunocompromised mice. In culture, most if not all of the HSC activity is detected in the EPCR+ subset, arguing for the stability of this marker on the surface of cultured cells, a feature not found with more recently described markers such as CD49f. Functionally EPCR is essential for human HSC activity in vivo. Cells engineered to express low EPCR expression proliferate normally in culture but lack the ability to confer long-term reconstitution. EPCR is thus a stable marker for human HSC. Its exploitation should open new possibilities in our effort to understand the molecular bases behind HSC self-renewal. Overall design: Examining 3 cellular subsets: EPCR+, EPCRlow, EPCR- derived form CD34+CD45RA- cord blood cells after 7 day expansion in UM171
EPCR expression marks UM171-expanded CD34<sup>+</sup> cord blood stem cells.
No sample metadata fields
View SamplesRNASeq data for mPB or CB-derived CD34+ exposed to UM171 Overall design: human mobilized peripheral blood or cord blood-derived CD34(+) cells were cultured for 16 hours with vehicle (DMSO), dose response of UM171 [11.9nM, 19nM, 30.5nM, 48.8nM, 78.1nM and 125nM], SR1 [500nM] and combination of( UM171 [48.8nM]+SR1 [500nM])
UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal.
No sample metadata fields
View SamplesPluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs). The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-ß) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs. This metabolic signature can be used to predict the onset of replicative senescence phenotypes. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging. Overall design: We did RNA-seq of dental pulp stem cells (DPSC) using our own approach (ID# 29, 43, 44, 45), as well as commercial DPSC and mesenchymal stem cells (MCS) from Lonza.
Metabolism as an early predictor of DPSCs aging.
Specimen part, Subject
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