Human skin-derived precursor cells (hSKP) are a stem cell population that represents key candidates for cell based-therapy. Inflammation, however, is often present in situations where cellular replacement therapy is required. These inflammatory conditions, and more specifically the presence of the cytokine interferon (IFN)-, might result in an increase of MHC class II antigens in hSKP-derived grafts and facilitate their rejection.
Human skin-derived precursor cells are poorly immunogenic and modulate the allogeneic immune response.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Variants of <i>DNMT3A</i> cause transcript-specific DNA methylation patterns and affect hematopoiesis.
Specimen part
View SamplesThe de novo DNA methyltransferase 3A (DNMT3A) plays a pivotal role in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing of DNMT3A has characteristic epigenetic and functional sequels. Various transcripts of DNMT3A were either knocked down or overexpressed in human hematopoietic stem and progenitor cells resulting in complementary and transcript-specific DNA methylation (DNAm) and gene expression changes. Our results demonstrate that different splice variants of DNMT3A have distinct epigenetic and functional sequels.
Variants of <i>DNMT3A</i> cause transcript-specific DNA methylation patterns and affect hematopoiesis.
Specimen part
View SamplesCompound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1.0 and 2.0 mg/mL), and 5-Fluorouracil (5-FU) was used to treat cells as a positive control. Cell proliferation and apoptosis activity were measured with XTT and Caspase-3 assays respectively. Transcriptome data of cells treated with CKI or 5-FU for 24 and 48 hours were acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment. Overall, we have comprehensively investigated the utility of transcriptome analysis with high-throughput sequencing to characterise the molecular response of cancer cells to a TCM drug, and provided a practical guideline for future molecular studies of TCM. Overall design: High-depth paired-end RNA-seq from MCF-7 cell line. Each sample contains 3 biological replicates.
Identification of candidate anti-cancer molecular mechanisms of Compound Kushen Injection using functional genomics.
No sample metadata fields
View SamplesNumerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) – a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission. In addition, we find that MEF2C regulates E/I synapse density predominantly as a cell-autonomous, transcriptional repressor. Analysis of differential gene expression in Mef2c mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the Mef2c mutant mice displayed numerous behaviors reminiscent of autism, ID and SCZ, suggesting that perturbing MEF2C function in neocortex can produce autistic- and ID-like behaviors in mice. Overall design: We carried out RNA-sequencing (RNA-seq) of somatosensory cortical tissue from control (Mef2cfl/fl) or Mef2c cKO (Mef2cfl/fl; Emx1-Cre) adult male mice. For the RNA-seq, three indipendent replicates were used for the mouse tissues.
MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.
Sex, Age, Specimen part, Cell line, Subject
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesGlucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
No sample metadata fields
View SamplesRecent reports have proposed a new paradigm for obtaining mature somatic cell types from fibroblasts without going through a pluripotent state, by briefly expressing canonical iPSC reprogramming factors Oct4, Sox2, Klf4 and c-Myc (abbreviated as OSKM), in cells expanded in lineage differentiation promoting conditions. Here we apply genetic lineage tracing for endogenous Nanog, Oct4 and X chromosome reactivation during OSKM induced trans-differentiation, as these molecular events mark final stages for acquisition of induced pluripotency. Remarkably, the vast majority of reprogrammed cardiomyocytes or neural stem cells derived from mouse fibroblasts via OSKM mediated trans-differentiation were attained after transient acquisition of pluripotency, and followed by rapid differentiation. Our findings underscore a molecular and functional coupling between inducing pluripotency and obtaining “trans-differentiated” somatic cells via OSKM induction, and have implications on defining molecular trajectories assumed during different cell reprogramming methods. Overall design: poly RNA-Seq was measured before, during and after conversion of mouse embryonic fibroblasts to neural stem cells using OSKM trans-differentiation method.
Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.
Specimen part
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