The role of the transcription factor EB (TFEB) in the control of cellular functions, including in vascular bed, is mostly thought to be the regulation of lysosomal biogenesis and autophagic flux. While this is its best-known function, we report here the ability of TFEB to orchestrate a non-canonical program involved in the control of cell-cycle and VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB deletion halts proliferation by inhibiting the CDK4/Rb pathway, which regulates the cell cycle G1-S transition. In an attempt to overcome this limit, cells compensate by increasing the amount of VEGFR2 on the plasma membrane through a microRNA-mediated mechanism and the control of its membrane trafficking. TFEB transactivates the miR-15a/16-1 cluster, which limits the stability of the VEGFR2 transcript, and negatively modulates the expression of MYO1C, which regulates VEGFR2 delivery to the cell surface. In TFEB knocked-down cells, the reduced and increased amount respectively of miR-15a/16-1 and MYO1C result in the overexpression on plasmamembrane of VEGFR2, which however shows low signaling strength. Using endothelial loss-of-function Tfeb mouse mutants, we present evidence of defects in fetal and newborn mouse vasculature caused by the reduced endothelial proliferation and by the anomalous function of VEGFR2 pathway. Thus, this study revealed a new and unreported function of TFEB that expands its role beyond the regulation of autophagic pathway in the vascular system.
TFEB controls vascular development by regulating the proliferation of endothelial cells.
Cell line
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Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
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View SamplesTemporally restricted feeding is known to impact the circadian clock. This dataset shows the effects of temporally restricted feeding on the hepatic transcriptome.
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
No sample metadata fields
View SamplesRestricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
No sample metadata fields
View SamplesCCAAT/enhancer binding protein ß (C/EBPß) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPß show protection against excitotoxic and ischemic CNS damage but the involvement of the various C/EBPß expressing cell types in this neuroprotective effect is not solved. Since C/EBPß-deficient microglia show attenuated neurotoxicity in culture we hypothesized that specific C/EBPß deficiency in microglia could be neuroprotective in vivo. In this study we have tested this hypothesis by generating mice with myeloid C/EBPß deficiency. Mice with myeloid C/EBPß deficiency were generated by crossing LysMCre and C/EBPßfl/fl mice . Primary microglial cultures from C/EBPßfl/fl (named here as WT) and LysMCre-C/EBPßfl/fl (named here as KO) mice were treated with lipopolysaccharide ± interferon ? (IFN?) for 6 h and gene expression was analyzed by RNA sequencing. LysMCre-C/EBPßfl/fl mice showed an efficiency of C/EBPß deletion of 100% in cultured microglia. Transcriptomic analysis of C/EBPß-deficient primary microglia revealed C/EBPß-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. This study provides new data that support a central role for C/EBPß in the biology of activated microglia. Overall design: LysMCre-C/EBPßfl/fl genotype (12 samples): 4 samples treated with LPS, 4 with LPS +IFNg, and 4 vehicle. C/EBPßfl/fl genotype (9 samples): 3 samples treated with LPS, 3 with LPS +IFNg, and 3 vehicle. Design Case (Treatment LPS or LPS +INF) control (No treatment or vehicle) in LysMCre-C/EBPßfl/fl genotype and in C/EBPßfl/fl genotype
RNA-Seq transcriptomic profiling of primary murine microglia treated with LPS or LPS + IFNγ.
No sample metadata fields
View SamplesTemporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
No sample metadata fields
View SamplesHigh-temporal resolution profiling was performed on mouse liver to detect rhythmic transcripts
Harmonics of circadian gene transcription in mammals.
No sample metadata fields
View SamplesHigh-temporal resolution profiling was performed on NIH3T3 fibroblasts to detect rhythmic transcripts
Harmonics of circadian gene transcription in mammals.
No sample metadata fields
View SamplesAFN-1252 is an inhibitor of fatty acid biosynthesis. Gene expression profiles were generated by microarray analysis of S. aureus cells following treatment with AFN-1252, an inhibitor of fatty acid synthesis.
Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252.
No sample metadata fields
View SamplesQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (IV) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 X 106 hMSCs were IV infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr but < 1,000 cells appeared in 6 other tissues. The hMSCs in lung up-regulated expression of multiple genes with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, IV hMSCs but not hMSCs transduced with TSG-6 siRNA decreased inflammatory responses, reduced infarct size, and improved cardiac function. IV administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest improvements in animal models and patients after IV infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
Specimen part, Disease
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