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SRP172777
Arabidopsis thaliana
6 Downloadable Samples
Illumina HiSeq 4000
Description
The polycomb repressive complex 2 (PRC2) regulates epigenetic gene repression in eukaryotes. Mechanisms controlling its developmental specificity and signal-responsiveness are poorly understood. Here, we identify an oxygen-sensitive N-terminal (N-) degron in the plant PRC2 subunit VERNALIZATION(VRN)2, a homolog of animal Su(z)12, that promotes its degradation via the N-end rule pathway. We provide evidence that this N-degron arose early during angiosperm evolution via gene duplication and N-terminal truncation, facilitating expansion of PRC2 function in flowering plants. We show that proteolysis via the N-end rule pathway prevents ectopic VRN2 accumulation, and that hypoxia and long-term cold exposure lead to increased VRN2 abundance, which we propose may be due to inhibition of VRN2 turnover via its N-degron. Furthermore, we identify an overlap in the transcriptional responses to hypoxia and prolonged cold, and show that VRN2 promotes tolerance to hypoxia. Our work reveals a mechanism for post-translational regulation of VRN2 stability that could potentially link environmental inputs to the epigenetic control of plant development. Overall design: RNA was extracted from non-vernalized (0v; C) or 4 week vernalized (4v; V) seedlings. Three biological replicates for each treatment were used for subsequent RNA sequencing
Publication Title
Oxygen-dependent proteolysis regulates the stability of angiosperm polycomb repressive complex 2 subunit VERNALIZATION 2.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Caenorhabditis elegans
- 11 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Oxidative stress may play a role in normal aging. SKN-1 is a transcription factor necessary for intestine development in Caenorhabditis elegans, which also regulates the response to oxidative stress post-embryonically. Using DNA microarrays, we found that oxidative stress induces the antioxidant response, the heat shock response, and detoxification genes, while the expression of genes involved in homeostasis, development, and reproduction were decreased. Both up-regulated and down-regulated genes can be wholly, partially, or not at all dependent on SKN-1 action. However, induction of the heat shock response by oxidative stress was not affected by SKN-1 removal.
Publication Title
Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.
Sample Metadata Fields
Sex, Age
View Samples- Phytophthora sojae, Glycine max
- 14 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
Total RNA extracted from Phytophthora sojae (strain P6497) and infected soybean hypocotyls (cultivar Harosoy) provided template for synthesis of cDNA probes used in the microarray hybridizations. Infected plant hypocotyls were sampled 6 h, 12 h, 24 h, and 48 h after inoculation. Mycelia were grown on synthetic media (H&S) or vegetable juice media (V8). Zoospores were sampled at 0 h, 2 h and 6 h after inducing encystment and germination by agitation.
Publication Title
The Phytophthora sojae avirulence locus Avr3c encodes a multi-copy RXLR effector with sequence polymorphisms among pathogen strains.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semi-allogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total PBMCs following delivery in healthy women were compared to those of non-pregnant control subjects. Interestingly, interferon stimulated genes (ISGs) encoding proteins such as IFIT1, IFIT2, and IFIT3, as well as signaling proteins such as STAT1, STAT2, and MAVS, were enriched postpartum. Antiviral genes were primarily expressed in CD14+ cells and could be stratified according to genetic variation at the interferon-3 gene (IFNL3, also named IL28B) single nucleotide polymorphism (SNP) rs12979860. Antiviral gene expression was sustained beyond six months following delivery in mothers with a CT or TT genotype but resembled baseline non-pregnant control levels following delivery in mothers with a CC genotype. CT and TT IFNL3 genotypes have been associated with persistent elevated ISG expression in individuals chronically infected with hepatitis C virus. Together these data suggest that postpartum, the normalization of the physiological rheostat controlling interferon signaling is dependent on IFNL3 genotype.
Publication Title
Prolonged activation of innate antiviral gene signature after childbirth is determined by IFNL3 genotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of the developmental stage at which they are isolated. Here we show that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse, dog and human tissues and its level of expression correlates with their myogenic competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3 abrogates mesoangioblast ability to cross the vessel wall and to engraft into damaged myofibers through the modulation of the junctional adhesion molecule-A. We conclude that PW1/Peg3 function is essential for conferring proper mesoangioblast competence and that the determination of PW1/Peg3 levels in human mesoangioblasts may serve as a biomarker to identify the best donor populations for therapeutic application in muscular dystrophies.
Publication Title
PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Several studies demonstrated IgVH mutation status and ZAP-70 expression as the most relevant prognostic markers in CLL, suggesting the separation of two patient subgroups: with good (MTZAP-70-) and poor prognosis (UMZAP-70+). We determined gene expression of B cells in 112 CLL patients divided into three classes: the first with IgVHMT and ZAP-70-, the second with IgVHUM and ZAP-70+, and the third included both IgVHUM ZAP-70- and IgVHMT ZAP-70+. We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid (glycerolipid/glycerophospholipid) metabolism overexpressed in UMZAP-70+. In addition, this study demonstrates the role of ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP-70+ in respect to MTZAP-70-. ARSD protein was found at significantly higher concentrations in UMZAP-70+ compared to MTZAP-70- CLL B cells and B cells from healthy individuals by Western blotting. Statistical analysis identified a strong correlation between ARSD and IgVH mutation status; ARSD protein level was associated with the requirement of therapy for CLL patients and for this purpose it is as good as IgVH mutational status. Our study highlights ARSD as a promising new prognostic factor in CLL and sphingolipid metabolism as a putative new biological mechanism in CLL.
Publication Title
Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The present research is devoted to the identification of gene(s) severely affected by LMNA mutations, leading to striated muscle laminopathies and more specifically the skeletal phenotype of Emery-Freifuss Muscular Dystrophy.
Publication Title
The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mesoangioblasts are stem/progenitor cells derived from a subset of pericytes expressing alkaline phosphatase. They have been shown to ameliorate muscular dystrophies (currently incurable diseases) in different animal models and are now undergoing clinical experimentation for Duchenne muscular dystrophy. We show here that patients affected by limb-girdle muscular dystrophy 2D (LGMD2D, characterized by -sarcoglycan deficit) have a reduction of this subset of pericytes and hence mesoangioblast could not be derived for cell therapy. Therefore, we reprogrammed LGMD2D fibroblasts and myoblasts to induced pluripotent stem cells (iPSCs) and developed a protocol for the derivation of mesoangioblast-like cells from them. These cells can be expanded and genetically corrected with a muscle-specific lentiviral vector expressing human -sarcoglycan. Upon transplantation into ad hoc generated -sarcoglycan-null immunodeficient mice, they generate myofibers expressing -sarcoglycan. This approach may be useful for muscular dystrophies that show a reduction of resident progenitors and provides evidence of pre-clinical safety and efficacy of disease-specific iPSCs.
Publication Title
Transplantation of genetically corrected human iPSC-derived progenitors in mice with limb-girdle muscular dystrophy.
Sample Metadata Fields
Sex, Specimen part
View Samples