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SRP131008
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2500
Description
The molecular chaperons FK506-binding proteins (Fkbps) comprise one of three families of peptidyl prolyl isomerases, which promote the transition between cis- and trans-conformations of peptidyl prolyl bonds. Mouse Fkbp family is composed of at least 15 members, but the functions of the large family in cell proliferation and differentiation remain elusive. During myoblast differentiation, the cells need to exit the cell cycle before fusion and terminal differentiation to form myotubes. The clear distinction between proliferation and differentiation provides an ideal model with which to investigate the roles of Fkbps in these two cell biological events. We found that depletion of FkbpC in mouse myoblasts delayed the exit from the cell cycle and expression of myotube-specific genes, whereas its overexpression caused opposite effects. At a mechanistic level, our study revealed a crucial function of FkbpC in Cdk4 activation during myoblast proliferation. Cdk4 undergoes conformational changes in the HSP90/Cdc37/Cdk4 complex as a prerequisite for activation through binding to CyclinD1 accompanied by phosphorylation. Our results showed that FkbpC depletion released Cdk4 from the HSP90 complex, which increased the Cdk4/CyclinD1 complex in myoblasts and sustained high levels of phosphorylated Cdk4 and Rb during differentiation. These results explain the delayed cell cycle exit and differentiation in the depleted cells. In addition, after synchronizing the cell cycle of myoblasts we found dynamic changes of the amounts of FkbpC and Cdk4 in the HSP90 complex during the G1/S transition. Knockout mice of FkbpC demonstrated delayed muscle regeneration after chemical damage, providing an in vivo evidence for the essential role of FkbpC in muscle differentiation. Collectively, our study uncovered FkbpC's critical function as a novel switch regulating the transition from proliferation to differentiation through controlling one of the central regulators of proliferation, Cdk4. Overall design: mRNA profiles of Fkbp4 knockdown, Fkbp5 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Publication Title
Promotion of Myoblast Differentiation by Fkbp5 via Cdk4 Isomerization.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Danio rerio
- 27 Downloadable Samples
- Illumina HiSeq 2500
Description
Acromegaly is a pathological condition due to excess growth hormone (GH) secretion. Acromegaly patients exhibit a deterioration of health and many associated complications, such as cardiovascular issues, arthritis, kidney diseases, muscular weakness, and colon cancer. Since these complications are generalized throughout the body, we investigated the effect of GH excess on cellular integrity. Here, we established stable acromegaly model zebrafish lines that overexpress tilapia GH and the red fluorescence protein (RFP) reporter gene for tracking GH gene expression throughout generations, and performed RNA-Seq data analysis from different organs. Intriguingly, heatmap and Expression2Kinases (X2K) analysis revealed the enrichment of DNA damage markers in various organs. Moreover, H2A.X immunostaining analysis in acromegaly zebrafish larvae and the adult acromegaly model brain and muscle showed a robust increase in the number of DNA-damaged cells. Using Gene Set Enrichment Analysis (GSEA), we found that the acromegaly zebrafish model had impaired DNA repair pathways in the liver, such as double-strand break (DSB), homologous recombination repair (HRR), non-homologous end joining (NHEJ), nucleotide excision repair (NER), and translesion synthesis (TLS). Interestingly, the impairment of DNA repair was even more prominent in acromegaly model than in aged zebrafish (three years old). Thus, our study demonstrates that affection of cellular integrity is characteristic of acromegaly Overall design: Total mRNA obtained from 1-years old acromegaly zebrafish model muscle, brain, kidney, liver and 3-day old larvae compared to wild-type (WT) zebrafish were generated by deep sequencing using Illumina.
Publication Title
An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking Cry2 display premature cell cycle exit and form short myotubes due to inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2-/- mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell cycle exit and inefficient cell fusion. This study uncovers a post-transcriptional regulation of myogenic differentiation by circadian rhythms. Overall design: mRNA profiles of Cry1 knockdown, Cry2 knockdown and control C2C12 cells at d0, d3 and d5 were generated by using Illumina HiSeq2500.
Publication Title
Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 25 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Muscle satellite cells are a self-renewing pool of stem cells that give rise to daughter myogenic precursor cells in adult skeletal muscle. Published and preliminary data indicated that MyoD and p53 genes are involved in satellite cell differentiation. We would like to know what downstream genes of both transcription factors are affected in satellite cell-derived myoblasts (MyoD-/-, p53 -/-).
Publication Title
MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TGF-b is an important pleiotropic cytokine with potent immunoregulatory properties. Although many previous reports have been proposed for the immunoregulatory functions of TGF-b on T cells, such as the suppression of cell proliferation, cytokine production and cytokine signaling, as well as the induction of apoptosis, it is not well elucidated whether the each effect of TGF-b on T cells is dependent on Smad signaling or Smad-independent other signaling pathways.
Publication Title
Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 1500
Description
Background: Blau syndrome, or early-onset sarcoidosis, is a juvenile-onset systemic granulomatosis associated with a mutation in Nucleotide-binding oligomerization domain 2 (NOD2). The underlying mechanisms of Blau syndrome leading to autoinflammation are still unclear, and there is currently no effective specific treatment for Blau syndrome. Objectives: To elucidate the mechanisms of autoinflammation in Blau syndrome, we sought to clarify the relation between disease associated-mutant NOD2 and the inflammatory response in human samples. Methods: Blau syndrome-specific induced pluripotent stem cells (iPSCs) lines were established. To precisely evaluate the in vitro phenotype of iPSC-derived cells, the disease-associated NOD2 mutation of iPSCs was corrected using a CRISPR/Cas9 system. We also introduced the same NOD2 mutation into a control iPSC line. These isogenic iPSCs were then differentiated into monocytic cell lineages, and the status of NF-?B pathway and proinflammatory cytokine secretion were investigated. Results: We focused on the signals that upregulate the expression of NOD2, especially IFN-? signaling. IFN-? treatment of NOD2-mutant macrophages induced ligand-independent NF-?B activation and proinflammatory cytokine production. IFN-? treatment acted as a priming signal through the up-regulation of NOD2 protein and recruitment of NOD2 on the basement membrane. Conversely, the production of proinflammatory cytokines by MDP, a ligand of NOD2, was decreased in mutant macrophages. Conclusions: Our data support the significance of ligand-independent autoinflammation in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific iPSC panel provides a useful platform for probing therapeutic and diagnostic clues for the treatment of Blau syndrome patients. Overall design: RNA-sequencing was conducted to identify the genes expressed in reponse to stimulation in different manners between WT and MT cells
Publication Title
Pluripotent stem cell models of Blau syndrome reveal an IFN-γ-dependent inflammatory response in macrophages.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Rattus norvegicus
- 31 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes,
Publication Title
Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mastication enhances brain function and even mental health, but little is known molecular basis underlying the effects of chewing on neural development in early childhood we conducted experiment with rats fed a with soft or hard chow diet immediately after weaning and investigated the expression of genes were investigated after another 8 days of breeding.
Publication Title
Short-term mastication after weaning upregulates GABAergic signalling and reduces dendritic spine in thalamus.
Sample Metadata Fields
Sex, Age
View Samples- Glycine max
- 8 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
Gene expression profiles in soybean seeds at 4 developmental stages, pod, bean 2 mm, bean 5 mm, and full-sized bean, were examined by DNA microarray analysis. Total genes of each samples were classified into 4 clusters according to developmental stages. Differentially expressed genes (DEGs) were extracted by comparing their expression in two adjacent stages, by using the rank product method.
Publication Title
Global gene expression profiles in developing soybean seeds.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of HEK293T cells overexpressing ZAPS (zinc finger antiviral protein, short form; NP_078901), which is a member of the PARP (poly (ADP-ribose) polymerase)-superfamily. Results of gene profiles provide insight into the role of ZAPS in innate immunity.
Publication Title
ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.
Sample Metadata Fields
Specimen part, Cell line
View Samples