BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells.
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ABSTRACT:
PROVIDER: PRJNA552990 | ENA |
REPOSITORIES: ENA
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Project description:In spite of lacking circadian rhythms, several master clock regulators are readily expressed in embryonic stem cells (ESCs). In particular, the role of Brain and Muscle ARNT-Like 1 (Bmal1, also known as Arntl) remains to be addressed. Here, we generated Bmal1 CRISPR/cas9 knock-out ESCs to elucidate the role of BMAL1 in pluripotency maintenance and differentiation. Our findings indicate that although BMAL1 is dispensable for ESC maintenance, it is required for proper differentiation. Moreover, we find that Bmal1 participates in the transcriptional regulation of lineage specification programs during differentiation and gastrulation in vitro. In particular, loss-of-function of Bmal1 changes the metabolic state of ESCs by promoting more oxidation at the expense of glycolysis. Our data points to a circadian clock-independent function of BMAL1 during early developmental stages, and will help in the understanding of the mechanisms that control exit from pluripotency and early cell-fate decisions.
2020-04-13 | GSE133908 | GEO
Project description:BMAL1 is essential for the regulation of circadian rhythms in differentiated cells and adult stem cells, but the molecular underpinnings of its function in pluripotent cells, which hold a great potential in regenerative medicine, remain to be addressed. Here, using transient and permanent loss-of-function approaches in mouse embryonic stem cells (ESCs), we reveal that although BMAL1 is dispensable for the maintenance of the pluripotent state, its depletion leads to deregulation of transcriptional programs linked to cell differentiation commitment. We further confirm that depletion of Bmal1 alters the differentiation potential of ESCs in vitro. Mechanistically, we demonstrate that BMAL1 participates in the regulation of energy metabolism maintaining a low mitochondrial function which is associated with pluripotency. Loss-of-function of Bmal1 leads to the deregulation of metabolic gene expression associated with a shift from glycolytic to oxidative metabolism. Our results highlight the important role that BMAL1 plays at the exit of pluripotency in vitro and provide evidence implicating a non-canonical circadian function of BMAL1 in the metabolic control for cell fate determination.
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Project description:Mice without cardiac Bmal1 function develop severe progressive heart failure with age. To examine the mechanism underlying the failing heart phenotype observed in heart-specific Bmal1 knockout mice, microarray analyses were performed. The analyses revealed that broad classes of genes regulating cellular energy metabolism were upregulated or downregulated in the heart tissues of heart-specific Bmal1 knockout mice compared with those of control animals. Heart total RNA extracted from six animals per genotype (control and heart-specific Bmal1 knockout) was pooled and then used for a microarray analysis.
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Project description:Vitamin D deficiency and mutations in Vitamin D Receptor (VDR) are associated with liver disease and obesity, but the functions of vitamin D signaling in metabolism are poorly understood. Though vitamin D signaling is best known for its functions in mineral homeostasis and skeleton calcification in terrestrial vertebrates, this is unlikely to be the evolutionary function of vitamin D signaling. We utilize tissue-specific genetic modulation of Vdr signaling to investigate the function of the vitamin D endocrine system in zebrafish. We find that hepatocyte Vdr regulates organismal response to nutritional cues and coordinates hepatic and organismal energy metabolism by balancing energy storage and tissue growth.
2023-04-20 | GSE217120 | GEO
Project description:Mice without cardiac Bmal1 function develop severe progressive heart failure with age. To examine the mechanism underlying the failing heart phenotype observed in heart-specific Bmal1 knockout mice, microarray analyses were performed. The analyses revealed that broad classes of genes regulating cellular energy metabolism were upregulated or downregulated in the heart tissues of heart-specific Bmal1 knockout mice compared with those of control animals.
2014-09-27 | GSE61787 | GEO
Project description:Functional and regulatory profiling of energy metabolism in fission yeast
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2014-02-21 | E-GEOD-55193 | biostudies-arrayexpress
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