Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products. Overall design: Single-cell mRNA sequencing of freshly isolated hematopoietic progenitors from human bone marrow. Sample HSC (Donor A) represents 1282 single cells. Sample MPP (Donor A) represents 215 single cells. Sample MLP (Donor A) represents 123 single cells. Sample PreB/NK (Donor A) represents 592 single cells. Sample MEP (Donor A) represents 1211 single cells. Sample CMP (Donor A) represents 1576 single cells. Sample GMP (Donor A) represents 1012 single cells. Sample Lin-CD34+CD164+ (Donor B) represents 6343 single cells. Sample Lin-CD34-CD164high (Donor B) represents 4434 single cells. Sample Lin-CD34lowCD164high (Donor B) represents 4266 single cells. Sample Lin-CD34-CD164low (Donor B) represents 358 single cells.
A comprehensive single cell transcriptional landscape of human hematopoietic progenitors.
Specimen part, Subject
View SamplesAffymetrix expression profiling was used to evaluate the association between IL13R2 expression, and mesenchymal, proneural, classical and neural signature genes expression for glioma subclasses defined by Verhaak et al (Cancer Cell; 2010).
Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.
Cell line, Treatment
View SamplesMuch has been learned about transcriptional cascades and networks from large-scale systems analyses of high-throughput data sets. However, analysis methods that optimize statistical power through simultaneous evaluation of thousands of ChIP-seq peaks or differentially expressed genes possess substantial limitations in their ability to uncover mechanistic principles of transcriptional control. By examining nascent transcript RNA-seq, ChIP-seq, and binding motif data sets from lipid A-stimulated macrophages with increased attention to the quantitative distribution of signals, we identified unexpected relationships between the in vivo binding properties of inducible transcription factors, motif strength, and transcription. Furthermore, rather than emphasizing common features of large clusters of co-regulated genes, our results highlight the extent to which unique mechanisms regulate individual genes with key biological functions. Our findings demonstrate the mechanistic value of stringent interrogation of well- defined sets of genes as a complement to broader systems analyses of transcriptional cascades and networks. Overall design: Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/-, Trif-/-, Irf3-/-, Ifnar-/-, and RelA-/- mice were stimulated with lipid A; C57Bl/6 macrophages were stimulated with lipid A in the presence of MAPK inhibitors or cycloheximide, or stimulated with PAM3CSK4 for 0, 15, 30, 60, and 120 minutes, or stimulated with lipid A for 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes. Two biological replicates were generated for each time point for each treatment type.
A Stringent Systems Approach Uncovers Gene-Specific Mechanisms Regulating Inflammation.
No sample metadata fields
View SamplesCutaneous sarcoidosis skin provides relatively non invasive access to granulomatous sarcoidosis tissue.
Molecular profiling and gene expression analysis in cutaneous sarcoidosis: the role of interleukin-12, interleukin-23, and the T-helper 17 pathway.
Subject
View SamplesThe transcriptional co-regulator IRF2BP1 gets de-SUMOylated after EGF treatment in Hela cells. SUMOylation of IRF2BP1 occurs at position K579.
Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.
Sex, Age, Specimen part, Disease, Time
View SamplesIn adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal but not perigonadal adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide DNA binding and RNA expression analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health. Overall design: Identification of adipocyte BCL6-regulated genes
Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity.
Sex, Specimen part, Subject
View Samplesobjection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases
Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.
Sex, Age, Specimen part, Disease, Time
View Samplesobjection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases
Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.
Sex, Age, Specimen part, Disease, Time
View SamplesObject: to understand Infliximab treatment effect on the molecular expression of tissue at disease site
Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.
Sex, Age, Specimen part, Disease, Time
View Samples