This SuperSeries is composed of the SubSeries listed below.
Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes.
Specimen part
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 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 SamplesFK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Specimen part, Treatment
View SamplesOct3/4, Sox2, Klf4, and c-Myc re-wire somatic cells to achieve induced pluripotency (iPS cells). However, subtle differences in reprogramming methodology may confound comparative studies of reprogramming-induced gene expression changes. We specifically focused on the design of polycistronic reprogramming constructs, which encode all four factors linked with 2A peptides. Notably, publically available cassettes were found to employ one of two Klf4 variants (Klf4S and Klf4L; GenBank Accession Nos: AAC52939.1 and AAC04892.1), differing only by nine N-terminal amino acids. In a polycistronic context, these two variants generated dissimilar protein stoichiometry, where Klf4L vectors produced more Klf4 protein than those encoding Klf4S.
KLF4 N-terminal variance modulates induced reprogramming to pluripotency.
Sex, 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 SamplesDietary restriction extends lifespan and delays the age-related physiological decline in many species. Intermittent fasting (IF) is one of the most effective dietary restriction regimens that extends lifespan in C. elegans and mammals1,2. In C. elegans, the FOXO transcription factor DAF-16 is implicated in fasting-induced gene expression changes and the longevity response to IF3; however, the mechanisms that sense and transduce fasting-stress stimuli have remained largely unknown. Here we show that a KGB-1/AP1 (activator protein 1) module is a key signalling pathway that mediates fasting-induced transcriptional changes and IF-induced longevity. Our promoter analysis coupled to genome-wide microarray results has shown that the AP-1-binding site, together with the FOXO-binding site, is highly over-represented in the promoter regions of fasting-induced genes. We find that JUN-1 (C. elegans c-Jun) and FOS-1 (C. elegans c-Fos), which constitute the AP-1 transcription factor complex, are required for IF-induced longevity. We also find that KGB-1 acts as a direct activator of JUN-1 and FOS-1, is activated in response to fasting, and, among the three C. elegans JNKs, is specifically required for IF-induced longevity. Our results demonstrate that most fasting-induced upregulated genes, including almost all of the DAF-16-dependent genes, require KGB-1 and JUN-1 function for their induction, and that the loss of kgb-1 suppresses the fasting-induced upregulation of DAF-16 target genes without affecting fasting-induced DAF-16 nuclear translocation. These findings identify the evolutionarily conserved JNK/AP-1 module as a key mediator of fasting-stress responses, and suggest a model in which two fasting-induced signalling pathways leading to DAF-16 nuclear translocation and KGB-1/AP-1 activation, respectively, integrate in the nucleus to coordinately mediate fasting-induced transcriptional changes and IF-induced longevity.
A fasting-responsive signaling pathway that extends life span in C. elegans.
Treatment
View SamplesIntermittent fasting is one of the most effective dietary restriction regimens that extend life-span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce fasting-stimulus have remained largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we have found that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acted as an activator of AP-1, and was activated in response to fasting. KGB-1 and AP-1 were involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhanced protein ubiquitination, and reduced protein carbonylation. Our results have thus identified a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity partly through regulating proteostasis.
A fasting-responsive signaling pathway that extends life span in C. elegans.
Treatment
View SamplesComparison of each cell mRNA expression pattern.
Direct conversion of human fibroblasts into functional osteoblasts by defined factors.
Specimen part
View SamplesSplicing profiles in pluripotent stem cells are different from those in somatic cells. Generally, alternative splicing is regulated by RNA binding proteins. To identify the candidate RNA-binding protein-encoding genes, we performed gene expression profiling experiments.
Global splicing pattern reversion during somatic cell reprogramming.
Specimen part, Cell line
View Samples