This SuperSeries is composed of the SubSeries listed below.
Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity.
Specimen part
View SamplesHematopoietic stem cell (HSC) transplantation has the potential to cure blood disorders but is limited by donor availability. Hence innovative approaches to engineer HSC are critically needed. HoxB4 over-expression in mouse embryonic stem cell-derived HSC (ESC-HSC) confers long-term engraftment, yet lacks efficient lymphogenesis. Transcriptome comparison of ESC-HSC versus embryo-derived HSC showed that ESC-HSC are deficient in expression programs activated by Notch. Therefore, we aim to improve ESC-HSC by further providing Notch signals through Notch1 intra-cellular domain transgene activation or by ligand stimulation. Here, we report that Notch-enhanced ESC-HSC (nESC-HSC) confer clonal multipotentiality with robust lymphopoiesis that endows adaptive immunity. Notably, nESC-HSC further evolve to a hybrid cell-type co-expressing gene regulatory networks of hematopoietic stem/progenitor cells and differentiated lineages at single-cell level that accounts for multipotentiality. Our work reveals a proof-of-concept model of HSC engineering by assembling self-renewing factor and lineage-guiding pathway into one product-cell that functionally recapitulate HSC in vivo. Overall design: The gene expression of murine hematopoietic stem cells, ESC, and HSC-like cells derived from differentiation of embryonic stem cells and subsequently transplanted were determined by single cell RNA-Seq.
Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity.
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View SamplesHematopoietic stem cell (HSC) transplantation has the potential to cure blood disorders but is limited by donor availability. Hence innovative approaches to engineer HSC are critically needed. HoxB4 over-expression in mouse embryonic stem cell-derived HSC (ESC-HSC) confers long-term engraftment, yet lacks efficient lymphogenesis. Transcriptome comparison of ESC-HSC versus embryo-derived HSC showed that ESC-HSC are deficient in expression programs activated by Notch. Therefore, we aim to improve ESC-HSC by further providing Notch signals through Notch1 intra-cellular domain transgene activation or by ligand stimulation. Here, we report that Notch-enhanced ESC-HSC (nESC-HSC) confer clonal multipotentiality with robust lymphopoiesis that endows adaptive immunity. Notably, nESC-HSC further evolve to a hybrid cell-type co-expressing gene regulatory networks of hematopoietic stem/progenitor cells and differentiated lineages at single-cell level that accounts for multipotentiality. Our work reveals a proof-of-concept model of HSC engineering by assembling self-renewing factor and lineage-guiding pathway into one product-cell that functionally recapitulate HSC in vivo.
Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity.
Specimen part
View SamplesHuman induced pluripotent stem (iPS) cells derived from somatic cells of patients hold great promise for modelling human diseases. Dermal fibroblasts are frequently used for reprogramming, but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPS cells from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPS lines are comparable to human embryonic stem (ES) cells with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation and differentiation potential. Analysis of Immunoglobulin and T-cell receptor gene rearrangement revealed that some of the PBMC iPS cells were derived from T-cells, documenting derivation of iPS cells from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe and efficient way of generating patient-specific iPS cells.
Reprogramming of T cells from human peripheral blood.
Specimen part, Cell line
View SamplesExpression profiling following depletion of Mediator Cdk8 module subunits Cdk8, Cyclin C (CycC), Med12 and Med13 72 hours after dsRNA treatment of Drosophila melanogaster S2 cells. Results provide insight into the role of individual Cdk8 module subunits in regulation of transcription.
Cyclin-dependent kinase 8 module expression profiling reveals requirement of mediator subunits 12 and 13 for transcription of Serpent-dependent innate immunity genes in Drosophila.
Specimen part
View SamplesThe experiments were performed to understand the molecular basis of plant growth promotion in rice by Rhodotorula mucilaginosa JGTA-S1, an endophytic yeast from Typha angustifolia
Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1.
Specimen part, Treatment, Time
View SamplesSIN3 is a master transcriptional scaffold protein. SIN3 interacts with RPD3 and other accessory proteins to form a histone modifying complex. A single Sin3A gene encodes multiple isoforms of SIN3, of which SIN3 187 and SIN3 220 are the predominant isoforms. Previous studies demonstrated that SIN3 isoforms play non-redundant roles during fly development. In the current study, we sought to investigate the genes regulated by SIN3 187. Overall design: S2 cells and cells carrying a stable transgene of SIN3 187HA (SIN3 187HA cells) were treated with 0.07 µM CuSO4. CuSO4 treatment led to ectopic expression of SIN3 187HA. S2 cells were used as a control. Following induction, total mRNA was extracted. mRNA profiling of these samples were performed by deep sequencing using Illumina Hiseq2500. Three biological replicates were performed.
Genome-wide studies reveal novel and distinct biological pathways regulated by SIN3 isoforms.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.
Specimen part, Disease, Disease stage, Cell line, Treatment, Subject, Time
View SamplesThe beneficial effects of glucocorticoids (GCs) in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis. Omics technologies such as DNA microarray analysis are widely used to study the changes in gene expression and have been successfully implemented in biomarker identification. In addition, time series studies of gene expression enable the identification of correlations between kinetic profiles of glucocorticoid receptor (GR) target genes and diverse modes of transcriptional regulation. This study presents a genome-wide microarray analysis of both our and published Affymetrix HG-U133 Plus 2.0 data in GCs-sensitive and -resistant ALL. GCs-sensitive CCRF-CEM-C7-14 cells were treated with dexamethasone at three time points (0 h, 2 h and 10 h). The treated samples were then compared to the control (0 h).
Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesThe beneficial effects of glucocorticoids (GCs) in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis. Omics technologies such as DNA microarray analysis are widely used to study the changes in gene expression and have been successfully implemented in biomarker identification. In addition, time series studies of gene expression enable the identification of correlations between kinetic profiles of glucocorticoid receptor (GR) target genes and diverse modes of transcriptional regulation. This study presents a genome-wide microarray analysis of both our and published Affymetrix HG-U133 Plus 2.0 data in GCs-sensitive and -resistant ALL. GCs-sensitive CCRF-CEM-C7-14 cells were treated with dexamethasone at three time points (0 h, 2 h and 10 h). The treated samples were then compared to the control (0 h).
Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.
Specimen part, Cell line, Treatment, Time
View Samples