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Characterisation of the epidermal diurnal transcriptome of mice with K14-Cre-driven Bmal1 knockout

ABSTRACT: To preserve a state of health, mammals employ an integrated network of molecular oscillators to drive daily rhythms of tissue-specific homeostatic processes. Importantly, the output, structure and coherence of this network is compromised by physiological ageing, disease and lifestyle changes. Yet, the key signalling nodes in this network, their underlying mechanisms of communication, and potential for therapeutic intervention, remain undefined. To dissect this system, we construct a minimal clock network consisting of two communicating nodes: the peripheral epidermal clock and central brain clock. We show that communication between the brain and epidermal clocks is sufficient for wild-type core clock activity and specific homeostatic processes, but inputs from other clock nodes are essential for full daily physiology. Unexpectedly, we find evidence that the epidermal clock selectively suppresses or interprets systemic signals to ensure coherence of specific homeostatic processes, identifying an unrecognised gatekeeper role for peripheral clocks. Together, we introduce a novel approach for dissecting a tissues daily physiology, and in turn identify key signalling nodes required to maintain epidermal homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE255474 | GEO | 2024/05/02

REPOSITORIES: GEO

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Characterisation of the epidermal diurnal transcriptome of mice with tissue-specific circadian clock activity [LD]

Project description:To preserve a state of health, mammals employ an integrated network of molecular oscillators to drive daily rhythms of tissue-specific homeostatic processes. Importantly, the output, structure and coherence of this network is compromised by physiological ageing, disease and lifestyle changes. Yet, the key signalling nodes in this network, their underlying mechanisms of communication, and potential for therapeutic intervention, remain undefined. To dissect this system, we construct a minimal clock network consisting of two communicating nodes: the peripheral epidermal clock and central brain clock. We show that communication between the brain and epidermal clocks is sufficient for wild-type core clock activity and specific homeostatic processes, but inputs from other clock nodes are essential for full daily physiology. Unexpectedly, we find evidence that the epidermal clock selectively suppresses or interprets systemic signals to ensure coherence of specific homeostatic processes, identifying an unrecognised gatekeeper role for peripheral clocks. Together, we introduce a novel approach for dissecting a tissues daily physiology, and in turn identify key signalling nodes required to maintain epidermal homeostasis.

2024-05-02 | GSE190032 | GEO

Characterisation of the epidermal circadian transcriptome of mice with tissue-specific circadian clock activity [DD]

Project description:To preserve a state of health, mammals employ an integrated network of molecular oscillators to drive daily rhythms of tissue-specific homeostatic processes. Importantly, the output, structure and coherence of this network is compromised by physiological ageing, disease and lifestyle changes. Yet, the key signalling nodes in this network, their underlying mechanisms of communication, and potential for therapeutic intervention, remain undefined. To dissect this system, we construct a minimal clock network consisting of two communicating nodes: the peripheral epidermal clock and central brain clock. We show that communication between the brain and epidermal clocks is sufficient for wiDD-type core clock activity and specific homeostatic processes, but inputs from other clock nodes are essential for full daily physiology. Unexpectedly, we find evidence that the epidermal clock selectively suppresses or interprets systemic signals to ensure coherence of specific homeostatic processes, identifying an unrecognised gatekeeper role for peripheral clocks. Together, we introduce a novel approach for dissecting a tissues daily physiology, and in turn identify key signalling nodes required to maintain epidermal homeostasis.

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Light can synchronise peripheral clocks autonomously from each other [darkness experiment (DD)]

Project description:Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues.

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Light can synchronise peripheral clocks autonomously from each other

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Integration of Feeding Behaviour by the Liver Circadian Clock Reveals Network Dependency of Metabolic Rhythms [RNA-seq]

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2021-06-10 | GSE167763 | GEO

Defining the Independence of the Liver Circadian Clock

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2019-06-13 | GSE132659 | GEO

Twenty-four hour rhythms in the absence of the clock gene Bmal1

Project description:Circadian (~24 hour) clocks exist in almost all types of living organism and play a fundamental role in regulating daily physiological and behavioural processes. The transcription factor BMAL1 (ARNTL) is thought to be one of the principal drivers of the molecular clock in mammals since its deletion abolishes 24-hour activity patterning, an important physiological output of the clockwork. However, whether or not Bmal1-/- mice can nevertheless display molecular 24-hour rhythms is unknown. Here, we determined whether Bmal1 function is necessary for daily molecular oscillations in two tissues – skin fibroblasts and liver. Unexpectedly, both tissues exhibited robust 24-hour oscillations over 2-3 days in the absence of any exogenous synchronizers such as daily light or temperature cycles. This demonstrates a competent 24-hour molecular pacemaker in Bmal1 knockouts. Indeed, molecular oscillations were pervasive throughout the transcriptome, proteome and phosphoproteome of Bmal1-/- mice. In particular, several proteins exhibited rhythmic phosphorylation in both Bmal1-proficient and -deficient cells, highlighting an unanticipated role for post-translational regulators in 24-hour rhythms in the absence of any known clock mechanisms.

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2017-11-23 | MSV000081736 | MassIVE

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