BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells

Ameneiro, Cristina; Moreira, Tiago; Fuentes-Iglesias, Alejandro; Coego, Alba; Garcia-Outeiral, Vera; Escudero, Adriana; Torrecilla, Daniel; Mulero‐Navarro, Sonia; Carvajal-González, José María; Guallar, Diana; Fidalgo, Miguel

doi:10.26508/lsa.201900534

Cited by 14 publications

(14 citation statements)

References 59 publications

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“…Bmal1 also plays an essential role in regulating the differentiation potential of embryonic stem cells (ESCs). Loss of Bmal1 function results in a shift from glycolytic to oxidative metabolism through the dysregulation of metabolic gene expression [76]. These results indicate that Bmal1 has a non-canonical circadian function, i.e., to regulate metabolic reprogramming in ESCs.…”

Section: Core Circadian Clock Genes and Metabolismmentioning

confidence: 89%

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Overview of the Circadian Clock in the Hair Follicle Cycle

et al. 2023

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The circadian clock adapts to the light–dark cycle and autonomously generates physiological and metabolic rhythmicity. Its activity depends on the central suprachiasmatic pacemaker. However, it also has an independent function in peripheral tissues such as the liver, adipose tissue, and skin, which integrate environmental signals and energy homeostasis. Hair follicles (HFs) maintain homeostasis through the HF cycle, which depends heavily on HF stem cell self-renewal and the related metabolic reprogramming. Studies have shown that circadian clock dysregulation in HFs perturbs cell cycle progression. Moreover, there is increasing evidence that the circadian clock exerts a significant influence on glucose metabolism, feeding/fasting, stem cell differentiation, and senescence. This suggests that circadian metabolic crosstalk plays an essential role in regulating HF regeneration. An improved understanding of the role of the circadian clock in HFs may facilitate the discovery of new drug targets for hair loss. Therefore, the present review provides a discussion of the relationship between the circadian clock and HF regeneration, mainly from the perspective of HF metabolism, and summarizes the current understanding of the mechanisms by which HFs function.

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Section: Core Circadian Clock Genes and Metabolismmentioning

confidence: 89%

“…The levels of ROS in tissues are closely associated with hair follicle regeneration. Loss of the circadian clock in stem cells can also result in a significant increase in ROS production [76]. Furthermore, normal mitochondrial function cannot be maintained in Bmal1-deficient, M1-activated macrophages [11,18,80,103].…”

Section: Discussionmentioning

confidence: 99%

Overview of the Circadian Clock in the Hair Follicle Cycle

et al. 2023

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“…Interestingly, coupling efficiency was increased in mice of the Bmal1 line when compared to mice of the Gpr88 line, presumably through reduced proton leakage in Bmal1 cKO and CTRL mice, indicating that the deletion of one copy of Bmal1 in the striatum is sufficient to cause these alterations. Conversely, a study on embryonic stem cells with a Bmal1 knockout revealed higher respiration accompanied by increased proton leakage and increased mitochondrial ROS production ( Ameneiro et al, 2020 ). The effects, however, may be linked to a specific role of Bmal1 on cell functions during embryogenesis.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2

Schöttner

Alonso²,

Button³

et al. 2022

Front. Physiol.

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The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.

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“…In mice with a dysfunctional circadian clock, the daily cycle of OXPHOS is abolished, suggesting that there is an intrinsic dependence of the mitochondrial respiration complexes on the circadian clockwork ( Neufeld-Cohen et al, 2016 ). Deletion of arntl in C2C12 myotubes causes a reduction of both OXPHOS and extracellular acidification rate (an indicator of glycolytic rate), but deletion in embryonic stem cells increases OXPHOS while reducing glycolytic rate ( Ameneiro et al, 2020 ; Peek et al, 2017 ). This suggests there is tissue specificity in the effect of ‘circadian clock knockout’ on mitochondrial responses.…”

Section: Introductionmentioning

confidence: 99%

Circadian coupling of mitochondria in a deep-diving mammal

Ciccone,

Kante,

Folkow

et al. 2024

Journal of Experimental Biology

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Regulation of mitochondrial oxidative phosphorylation is essential to match energy supply to changing cellular energy demands, and to cope with periods of hypoxia. Recent work implicates the circadian molecular clock in control of mitochondrial function and hypoxia sensing. Since diving mammals experience intermittent episodes of severe hypoxia, with diel patterning in dive depth and duration, it is interesting to consider circadian - mitochondrial interaction in this group. Here we demonstrate that the hooded seal (Cystophora cristata), a deep diving Arctic pinniped, shows strong daily patterning of diving behaviour in the wild. Cultures of hooded seal skin fibroblasts exhibit robust circadian oscillation of the core clock genes per2 and arntl. In liver tissue collected from captive hooded seals, expression of arntl was some 4-fold higher in the middle of night than in the middle of the day. To explore the clock-mitochondria relationship, we measured the mitochondrial oxygen consumption in synchronized hooded seal skin fibroblasts and found a circadian variation in mitochondrial activity, with higher coupling efficiency of complex I coinciding with the trough of arntl expression. These results open the way for further studies of circadian - hypoxia interactions in pinnipeds during diving.

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BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells

Cited by 14 publications

References 59 publications

Overview of the Circadian Clock in the Hair Follicle Cycle

Overview of the Circadian Clock in the Hair Follicle Cycle

Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of Bmal1 and Per2

Circadian coupling of mitochondria in a deep-diving mammal

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