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SRP173650
Homo sapiens
28 Downloadable Samples
Illumina HiSeq 2500
Description
Pluripotent 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.
Publication Title
Metabolism as an early predictor of DPSCs aging.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from cardiogenic or hemogenic mesoderm. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified novel candidate regulators of mesodermal lineage determination. HOPX, a non-DNA binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. We used HOPX reporter and knockout hESCs, as well as hopx loss of function studies in zebrafish, to show the requirement of HOPX in vivo and in vitro in hemato-endothelial lineage specification. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis acting at least in part through suppression of Wnt/ß-catenin signaling. Single cell RNA-seq data during mouse hematopoietic development in vivo confirm a role for HOPX in hematopoietic fate. Taken together, we show that HOPX is a novel regulator of hemato-endothelial fate specification in vitro and in vivo that functionally regulates Wnt signaling to modulate primitive hematopoiesis. Overall design: 2 biological replicates were isolated from cardiac progenitor cells (CPCs) and endothelial populations derived from cardiogenic mesoderm (C-ECs) and hemogenic mesoderm (H-ECs). RNA-seq and ChIP-seq (H3K4me3 and H3K27me3) was performed for each replicate.
Publication Title
Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.
Publication Title
Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 179 Downloadable Samples
- NextSeq 500
Description
Lung development and function arises from the interactions between diverse cell types and lineages. Using single cell RNA-seq we characterize the cellular composition of the lung during development and identify vast dynamics in both the composition of cells and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, ILC and basophils. Using IL33-receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and GM-CSF, characterized by unique signaling of cytokines and growth factors important for stromal, epithelial and myeloid cell fates. Antibody depletion strategies, diphtheria toxin–mediated selective depletion of basophils, and co-culture studies, show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole tissue cell interaction analysis on the single cell level can broaden our understanding of cellular networks in health and disease. Overall design: Transcriptional profiling of single cells from the different timepoints of lung development, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500 metadata.txt: Meta data file associating each single cell with its amplification batch and index sorting readouts
Publication Title
Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-nave dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. .
Publication Title
Link between epigenomic alterations and genome-wide aberrant transcriptional response to allergen in dendritic cells conveying maternal asthma risk.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
XRN2 is a conserved 5’-->3’ exoribonuclease that complexes with XTB-domain containing proteins. Thus, in Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes XRN2 to retain its activity. XRN2 activity is also promoted by 3''(2''),5''-bisphosphate nucleotidase 1 (BPNT1) through its hydrolysis of 3’-phosphoadenosine-5''-bisphosphate (PAP), an endogenous XRN inhibitor. Here, we find through unbiased screening that loss of bpnt-1 function suppresses lethality caused by paxt-1 deletion. This unexpected finding is explained by XRN2 autoregulation, which occurs through repression of a cryptic promoter activity and destabilization of the xrn-2 transcript. Autoregulation appears to be triggered at different thresholds of XRN2 inactivation, such that more robust XRN2 perturbation, by elimination of both PAXT-1 and BPNT1, is less detrimental to worm viability than absence of PAXT-1 alone. Like more than 15% of C. elegans genes, xrn-2 occurs in an operon, and we identify additional operons under its control, consistent with a broader function of XRN2 in polycistronic gene regulation. Regulation occurs through intercistronic regions that link genes in an operon, but similar mechanisms may allow XRN2 to operate on monocistronic genes in organisms lacking operons. Overall design: Wild-type C. elegans worms were subjected to mock or xrn-2 RNAi from L1 to L4 stage at 20°C. Total RNA was extracted from the worms, and polyadenylated RNA was analyzed.
Publication Title
XRN2 Autoregulation and Control of Polycistronic Gene Expresssion in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal is to investigate gene regulation in endometrial stromal cells expressing the Notch ligand Jag1.
Publication Title
Notch ligand-dependent gene expression in human endometrial stromal cells.
Sample Metadata Fields
Specimen part
View Samples- Glycine max
- 6 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
The seed coat of black (iRT) soybean with the dominant R allele begins to accumulate cyanic pigments at the transition stage of seed development (300 400 mg fresh seed weight), whereas the brown (irT) nearly-isogenic seed coat with the recessive r allele lacks cyanic pigments at all stages of seed development.
Publication Title
Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max) seed coats enabling the identification of pigment isogenes.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
microRNAs (miRNAs) constitute a class of small non-coding RNAs (~22nt). They are thought to be generally stable with half-lives of many hours or even days. However, several miRNAs have been reported to decay rapidly in specific situations. In order to examine miRNA stability on a global scale, we quantify relative decay rates of miRNA in first larval stage C. elegans worms that are treated with a transcription inhibitor alpha-amanitin by deep sequencing. Several miRNAs including members of the miR-35 and miR-51 families exhibit accelerated decay. Moreover, biogenesis of miRNAs involves generation of a miRNA duplex intermediate consisting of the miRNA guide strand (miR) and the miRNA passenger strand (miR*). miR and miR* names were originally assigned based on the relative abundance of each strand, with the less abundant strand presumed to be inactive, and thus the miR*. However, subsequent research showed that at least individual miR*s can have biological activity. Our sequencing data reveal that miR*s, operationally defined on the basis of their relative abundance at time point t=1h, are substantially less stable than miRs. This would appear to support the notion that miR*s mainly constitute processing byproducts rather than a less abundant class of functional miRNAs. Overall design: Examination of microRNA decay rates in the first larval stage C. elegans worms.
Publication Title
Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples