Circadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the post-transcriptional regulation of Clock subsequent to the cellular differentiation for the emergence of robust circadian clock oscillation in mouse fetal hearts and mESCs (mouse embryonic stem cells). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable in around embryonic day (E) 10 whereas robust oscillation was clearly visible in E18 heart. Temporal RNA-seq analysis using mouse fetal hearts reveals much fewer rhythmic genes in E10-12 hearts (63, no clock genes) than E17-19 (483 genes), indicating the lack of functional circadian clocks in E10 mouse fetal hearts. In both mESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was at least partially due to miRNA-mediated translational suppression of CLOCK. The CLOCK protein is required for the robust molecular oscillation in differentiated cells, and the post-transcriptional regulation of Clock plays a key role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.
Involvement of posttranscriptional regulation of <i>Clock</i> in the emergence of circadian clock oscillation during mouse development.
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View SamplesWe used microarrays to select the genes associated glioma patients survival.
Gene expression signature-based prognostic risk score in patients with glioblastoma.
Sex, Age, Disease, Disease stage
View SamplesThis study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed.
Gene expression signature-based prognostic risk score in patients with primary central nervous system lymphoma.
Sex, Age, Specimen part, Disease, Disease stage
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Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes.
Specimen part
View SamplesRecently, acute kidney injury (AKI) is thought to develop a predisposition toward chronic kidney disease. But the detailed mechanism of the disease progression after AKI is unknown. We made two ischemia-reperfusion injury (IRI) mice models, repaired kidney model and atrophic kidney model, and studied the mechanism that kidney after IRI became atrophy. We found that the atrophy kidney model had two peaks of apoptosis 3 and 14 days after IRI, whereas the repaired kidney model had only one apoptosis peak 3 days after IRI. We showed that the second apoptosis is responsible for the kidney atrophy. Moreover, apoptotic ligands, TNF and FasL were upregulated at the same time of two apoptosis peaks on the atrophic kidney, and blockade of them before IRI prevented kidney from falling into atrophy. Surprisingly, inhibition of the second apoptosis by anti-TNF antibody protected from renal atrophy. We propose that apoptosis might play a major role in AKI progression and blockade of TNF after IRI will be a new therapeutic approach for AKI.
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Sex
View SamplesComparasion of each cell mRNA expression pattern
Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes.
Specimen part
View SamplesComparison of each cell mRNA expression pattern.
Direct conversion of human fibroblasts into functional osteoblasts by defined factors.
Specimen part
View SamplesComparason of each cell mRNA expression pattern
Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal.
Specimen part
View SamplesRSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL). RSK2-Ser227 in the N-terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL-derived cell lines and in tumor tissues derived from five MCL patients. BI-D1870, an inhibitor specific to RSK2-NTKD, caused RSK2-Ser227 dephosphorylation, and thereby, induced dose-dependent growth inhibition via G2/M cell cycle blockade and apoptosis. Comparative gene expression profiling of the MCL-derived cell lines showed that inhibition of RSK2-Ser227 by BI-D1870 caused downregulation of oncogenes, such c-MYC and MYB; anti-apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3 and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B and BLNK. These findings show that targeting of RSK2-Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis.
No associated publication
Cell line, Treatment
View SamplesComparasion of each cell mRNA expression pattern
Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes.
Specimen part
View Samples