Plant compensatory responses depends on transcriptional reprogramming. We used microarray analysis to understand the differential gene expression pattern between clipped (herbivore browsed)
Overcompensation in response to herbivory in Arabidopsis thaliana: the role of glucose-6-phosphate dehydrogenase and the oxidative pentose-phosphate pathway.
Specimen part
View SamplesOur understanding of how mesodermal tissue is formed, has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESC) is initiated by Epithelial to Mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that CD326negCD56+ cells, generated from hESC in the presence of activin A, BMP4, VEGF and FGF2, represent a novel, multi-potent mesoderm-committed progenitor population. CD326negCD56+ progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle and cardiomyocytes, while lacking the pluripotency of hESC. CD326negCD56+ cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a novel approach to study how germ layer specification is regulated, and offer a unique target for tissue engineering.
Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.
Cell line
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 SamplesHomodimerization of Mpl can also be accomplished in the absence of Tpo, by binding of a synthetic ligand (Chemical inducer of dimerization, CID) to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. In contrast to Tpo stimulation, F36VMpl dimerization in human CD34+ progenitor cells generates robust erythropoiesis.
Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.
Specimen part
View SamplesMotivation and design: Renal tubulointerstitial injury is an important determinant of chronic kidney disease (CKD) progression, yet treatment is limited to renin angiotensin system blockade. Accordingly, we performed global expression profiling in a 2 × 2 factorial design (N = 8 in each group) on RNA extracted from male Col4a3–/– mice and littermate controls on a 129X1/SvJ background at 4 and 7 weeks of age. Col4a3–/– mice have a mutation in the gene encoding the α3 chain of type IV collagen, associated with proteinuria and progressive loss of kidney function. We analyzed expression with Affymetrix GeneChip Mouse Gene 2.0 ST Arrays and derived a novel CKD progression signature based on aging and disease in Col4a3–/– mice. Using our progression signature, we sought to repurpose existing drugs for the treatment of progressive CKD.
Connectivity mapping of a chronic kidney disease progression signature identified lysine deacetylases as novel therapeutic targets.
Sex, Age, Specimen part
View SamplesAnalysis of TH17 cells redirected with chimeric antigen receptors (CAR) expressing various signaling domains (including CD28, 4-1BB and ICOS) after surrogate antigen stimulation.
ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A molecular signature of proteinuria in glomerulonephritis.
Specimen part
View SamplesBoth a lack of biomarkers and relatively ineffective treatments constitute impediments to management of lupus nephritis (LN). Here we used gene expression microarrays to contrast the transcriptomic profiles of active SLE patients with and without LN to identify potential biomarkers for LN. RNA isolated from whole peripheral blood of active SLE patients was used for transcriptomic profiling and the data analyzed by linear modeling, with corrections for multiple testing. Results were validated in a second cohort of SLE patients, using NanoString technology. The majority of genes demonstrating altered mRNA abundance between patients with and without LN were neutrophil-related. Findings in the validation cohort confirmed this observation and showed that the levels of gene expression in renal remission were similar to active patients without LN. In secondary analyses, gene expression correlated with disease activity, hematuria and proteinuria, but not renal biopsy changes. As expression levels of the individual genes correlated strongly with each other, a composite neutrophil score was generated by summing all levels before examining additional correlations. There was a modest correlation between the neutrophil score and the blood neutrophil count, which was largely driven by the dose of steroids and not the proportion of low density and/or activated neutrophils. Analysis of longitudinal data revealed no correlation between baseline neutrophil score or changes over the first year of follow-up with subsequent renal flare or treatment outcomes, respectively. The findings argue that although the neutrophil score is associated with LN, its clinical utility as a biomarker may be limited.
Identification of a neutrophil-related gene expression signature that is enriched in adult systemic lupus erythematosus patients with active nephritis: Clinical/pathologic associations and etiologic mechanisms.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesProteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.
A molecular signature of proteinuria in glomerulonephritis.
Specimen part
View SamplesProteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.
A molecular signature of proteinuria in glomerulonephritis.
Specimen part
View Samples