This SuperSeries is composed of the SubSeries listed below.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Specimen part, Cell line
View SamplesThe heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show when depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Cell line
View SamplesSTN7-dependent phosphorylation of an as yet unknown thylakoid protein triggers the signaling events associated with the long-term acclimatory response (LTR). The LTR-associated signaling events regulate the expression of photosynthesis-related genes on the post-transcriptional level (nucleus), as indicated by transcript profiling in LTR mutants.
Arabidopsis STN7 kinase provides a link between short- and long-term photosynthetic acclimation.
Specimen part
View SamplesAcute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.
Specimen part, Disease
View SamplesWe utilized our transgenic Fgd5-mCherry mouse to sort and RNAseq for HSCs under acute immune activation (with pIC) to reveal a complex cell cycle gene expression and an upregulated IFN I/II signature Overall design: RNAseq of bone marrow Lineage-Sca1+cKit+CD150+mCherry+ cells (1000) 24hrs after pIC was administered and control (PBS treated)
Identification of immune-activated hematopoietic stem cells.
Specimen part, Cell line, Treatment, Subject
View SamplesAlthough a large set of data is available concerning organogenesis in animal models, information remains scarce on human organogenesis. In this work, we performed temporal mapping of human fetal pancreatic organogenesis using cell surface markers. We demonstrate that in the human fetal pancreas at 7 weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate either into the acinar, ductal and endocrine lineages. Development towards the acinar lineage is paralleled by a substantial increase in GP2 expression. Conversely, a subset of the multipotent GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, an early marker of endocrine differentiation. Endocrine maturation will progress by up-regulating SUSD2 and lowering ECAD levels. Finally, we show that in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work constitutes a powerful approach to more precisely define intermediate cell population during conversion of multipotent progenitors into the 3 main human pancreatic cell types (acinar, ductal and endocrine) in vivo. As such, the data pave the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.
Reconstructing human pancreatic differentiation by mapping specific cell populations during development.
Specimen part
View SamplesThe species Staphylococcus (S.) aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). While these egc superantigens are far more prevalent in clinical S. aureus isolates than non-egc superantigens, they are not a prominent cause of toxic shock. Moreover, neutralizing antibodies against egc superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation we have tested two non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic properties and drive the immune system into different directions; 2) egc and non-egc-superantigens are released by S. aureus under different conditions, which shape the immune response.
Immune cell activation by enterotoxin gene cluster (egc)-encoded and non-egc superantigens from Staphylococcus aureus.
No sample metadata fields
View SamplesWe here addressed the question whether the unique capacity of mesenchymal stromal/stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense pathogen associated molecular pattern (PAMP) and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs which had been primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurred, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS treated MSCs as deduced from RNA-seq analysis and its validation. A network of genes mediating the adaptive response through the TLR-4 pathway responsible for neutrophil activation (GCP- 2, ENA-78, IL-1ß IL-8) and MSC protection (SOX6) profoundly contributes to enhanced wound healing. In fact, silencing of either TRL-4, or IRAK3, a downstream effector of TRL-4, or SOX6 suppressed wound healing most likely due to suppression of neutrophil extracellular trap formation and suppression of the enhanced microbicidal release of reactive oxygen species (ROS), key features of neutrophil activation. This previously unreported results uncover SOX6 which protects MSCs at the wound site from enhanced oxidative stress. This unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds. Overall design: Transcriptome profiling of MSCs
TLR4-dependent shaping of the wound site by MSCs accelerates wound healing.
Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sex, Specimen part, Subject
View SamplesIntraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells.
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation.
Sex, Specimen part, Subject
View Samples