We and others have previously observed that adipocytes and preadipocytes taken from different adipose tissue depots are characterized by differential expression of developmental and patterning genes (Dankel et al., 2010; Ferrer-Lorente et al., 2014; Gesta et al., 2006; Lee et al., 2017a; Lee et al., 2013; Macotela et al., 2012; Tchkonia et al., 2007; Yamamoto et al., 2010). To investigate how adipocyte heterogeneity and differences in the expression of developmental genes might impact the biology of adipocytes and preadipocytes, we created preadipocyte cell lines from the stromovascular fraction (SVF) isolated from the scapular white, inguinal, perigonadal, perirenal, and mesenteric fat pads of 6-week old male Immortomouse (Jat et al., 1991).During routine culture of the subcutaneous and visceral/perigonadal clonal cell lines, we observed extreme variation in media acidification rates that was unrelated to the fat pad of origin, the differentiation capacity of the cells, or the rate of their proliferation, suggesting metabolic heterogeneity. To further investigate this possibility, 24 clonal cell lines (12 each from subcutaneous and perigonadal fat) were selected based on variable media acidification rates, and their mRNA expression pattern determined by microarray analysis. The expression data was clustered using three different algorythms, and the consensus was used to categorize each type of adipose tissue.
Developmental and functional heterogeneity of white adipocytes within a single fat depot.
Specimen part, Cell line
View SamplesTo investigate the effects of BCL11B on T-cell differentiation, we performed gain of function studies in cells with a T-lineage differentiation arrest, namely T-ALL cells. Gene expression profiling by RNA-Seq demonstrated that BCL11B overexpression induced transcriptional changes consistent with T-cell differentiation as early as 72 hours after transduction, indicating a rapid regulatory effect of BCL11B on the T-lineage transcriptional program and supporting an important role for BCL11B in human T-cell differentiation. Overall design: T-ALL cells were transduced with a BCL11B-GFP expression vector (overexpressing cells) or an empty GFP vector (control cells). GFP+ cells were isolated by fluorescence activation cell sorting (FACS) at 72 hours post transduction and analyzed by RNA-Seq to determine the effect of BCL11B on the transcriptome of T-ALL cells.
The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.
Subject
View SamplesTo elucidate the transcriptional ‘landscape’ that regulates human lymphoid commitment during postnatal life, we used RNA sequencing to assemble the long non-coding transcriptome across human bone marrow and thymic progenitor cells spanning the earliest stages of B lymphoid and T lymphoid specification. Over 3,000 genes encoding previously unknown long non-coding RNA (lncRNAs) were revealed through the analysis of these rare populations. Lymphoid commitment was characterized by lncRNA expression patterns that were highly stage specific and were more lineage specific than those of protein-coding genes. Protein-coding genes co-expressed with neighboring lncRNA genes showed enrichment for ontologies related to lymphoid differentiation. The exquisite cell-type specificity of global lncRNA expression patterns independently revealed new developmental relationships among the earliest progenitor cells in the human bone marrow and thymus. Overall design: We performed RNA-Seq of 10 distinct cell types isolated by fluorescence activated cell sorting (FACS). From BM, we isolated CD34+CD38neglinneg cells, a population highly enriched for HSC, as well as three lymphoid progenitor populations; LMPP (CD34+CD45RA+CD38+CD10neg CD62Lhilinneg), CLP (CD34+CD38+CD10+CD45RA+linneg ) and fully B cell committed progenitors (BCP, CD34+CD38+CD19+). From thymus we isolated three CD34+ subsets; Thy1 (CD34+CD7neg CD1aneg CD4negCD8neg), Thy2 (CD34+CD7+CD1aneg CD4negCD8neg), and Thy 3 (CD34+CD7+CD1a+CD4negCD8neg), as well as fully T cell committed populations CD4+CD8+ (Thy 4), CD3+CD4+CD8neg (Thy5) and CD3+CD4neg CD8+ (Thy6).
Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineages.
No sample metadata fields
View SamplesMore than 200 direct CodY target genes in Staphylococcus aureus were identified by genome-wide analysis of in vitro DNA binding. This analysis, which was confirmed for some genes by DNase I footprinting assays, revealed that CodY is a direct regulator of numerous transcription units associated with amino acid biosynthesis, transport of macromolecules and virulence. The virulence genes regulated by CodY fell into three groups. One group was dependent on the Agr system for its expression; these genes were indirectly regulated by CodY through its repression of the agr locus. A second group was regulated directly by CodY. The third group, which includes genes for alpha-toxin and capsule synthesis, was regulated by CodY in two ways, i.e., by direct repression and by repression of the agr locus. Since S. aureus CodY was activated in vitro by the branched chain amino acids and GTP, CodY appears to link changes in intracellular metabolite pools with the induction of numerous adaptive responses, including virulence.
Direct targets of CodY in Staphylococcus aureus.
No sample metadata fields
View SamplesmRNA microarray analysis of bone marrow derived macrophages treated under four conditions, including Nave (N). Bone marrow derived macrophages (BMDM) were derived from the bone marrow of mice and cultured in the presence of PAO, IFN-gamma, or lipopolysaccharide (LPS). Profiled groups include Naive, LPS, IFN, PAO.
Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.
Sex, Specimen part
View SamplesWe performed the integrative transcriptome analysis of human esophageal squamous cell carcinoma (ESCC) using Illumina high-throughput sequencing. A total of 187 million 38bp sequencing reads were generated containing 7 billion bases for three pairs of matched patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues. By investigating the digital gene expression profiling, we found 1425 genes significantly differentially expressed and detected more than 9000 SNPs across all six samples. We also identified protein tyrosine kinase 6 (PTK6) as a novel tumor suppressor gene, which is critical in ESCC development. Overall design: Analysis of whole transcriptome from 3 paired patient-derived ESCC clinical specimens and their adjacent non-tumorous tissues.
Transcriptome profiling of esophageal squamous cell carcinoma reveals a long noncoding RNA acting as a tumor suppressor.
No sample metadata fields
View SamplesLiver X Receptors (LXRa and ß) are ligand-activated transcription factors that play a key role in the control of lipid homeostasis, as well as modulation of immunity and inflammation. LXR activity can be regulated by posttranslational modifications, such as phosphorylation. This study aims to assess changes in the hepatic transcriptional profiles of mice that carry a whole-body phosphorylation deficient knock in mutant of LXRa (S196A) compared to wild-type (WT) upon being fed a HFHC diet. Overall design: Liver mRNA profiles of either wild-type (WT) or LXRa-S196A female mice after being fed a High Fat-High Cholesterol diet for 6 weeks. Three biological replicate samples for each group are included. WT samples are used as controls.
Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease.
Sex, Specimen part, Cell line, Subject
View SamplesLiver X Receptors (LXRa and ß) are ligand-activated transcription factors that play a key role in the control of lipid homeostasis, as well as modulation of immunity and inflammation. LXR activity can be regulated by posttranslational modifications, such as phosphorylation. This study aims to assess changes in the hepatic transcriptional profiles of mice that carry a whole-body phosphorylation deficient knock in mutant of LXRa (S196A) compared to wild-type (WT) fed a chow diet. Overall design: Liver mRNA profiles of either wild-type (WT) or LXRa-S196A 16-week old female mice on a chow diet. Three biological replicate samples for each group are included. WT samples are used as controls.
Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease.
Specimen part, Cell line, Subject
View SamplesThe liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human fetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of fetal liver and maintain a unique transcriptional profile distinct from fetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogenicity within the EpCAM+ population of freshly isolated fetal and adult human liver reveals diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolated fetal HHyPs and confirmed their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles. Overall design: Primary samples from 5 2nd trimester human fetal livers and 3 uninjured adult human livers for single cell RNA sequencing by Smartseq2.
Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.
Age, Specimen part
View Samples