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.
Promotion of Myoblast Differentiation by Fkbp5 via Cdk4 Isomerization.
Specimen part, Cell line, Subject, Time
View SamplesCircadian 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.
Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.
Specimen part, Cell line, Subject
View SamplesMuscle 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 -/-).
MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.
No sample metadata fields
View SamplesTo elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes,
Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.
No sample metadata fields
View SamplesMastication 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.
Short-term mastication after weaning upregulates GABAergic signalling and reduces dendritic spine in thalamus.
Sex, Age
View SamplesGene 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.
Global gene expression profiles in developing soybean seeds.
No sample metadata fields
View SamplesGlobal analyses on gene expression profiles in two soybean species, Nanahomare and Tamahomare was performed using DNA microarray technique. Nanahomare is glycinin deficient species, and is high in free amino acid content. Tamahomare is parent species of Nanahomare.
Expression of the stress-related genes for glutathione S-transferase and ascorbate peroxidase in the most-glycinin-deficient soybean cultivar Tousan205 during seed maturation.
No sample metadata fields
View SamplesTo analyze the gene expression alteration after stroke, we used Middle Cerebral Artery Occlusion model of rats. By comparing with Sham operated rats, we extracted the mRNAs whose expressions are alterated by stroke.
Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood.
Sex, Age, Specimen part
View SamplesAnalysis of gastrocnemius from male wild type(WT) and Skn-1-deficient mice. Skn-1-deficient mice have reduced body weight with low body fat due to increased energy expenditure.
Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1-deficient Mice.
Sex, Specimen part, Time
View SamplesWe observed that follicular dendritic cell line induced a new type of CD11b+ myeloid cells (FDMCs) when cultured with a lineage-negative c-kit+ population from mouse spleen cells.
CSF-1 receptor-mediated differentiation of a new type of monocytic cell with B cell-stimulating activity: its selective dependence on IL-34.
No sample metadata fields
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