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. Overall design: Determining the epidermal circadian transcriptome in the presence or absence of non-epidermal clocks after 6-7 days in complete darkness (DD).
BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.
Age, Specimen part, Cell line, Subject
View SamplesOrganisms 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. Overall design: Determining the epidermal circadian transcriptome in the presence or absence of non-epidermal clocks under light entrainment (LD).
BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.
Age, Specimen part, Cell line, Subject
View SamplesTo explore how PKC regulates tumorigenesis, we performed mRNA expression analysis of four KRAS mutant NSCLC cell lines that stably express scrambled shRNA or PKC targeted shRNA
PKCδ regulates integrin αVβ3 expression and transformed growth of K-ras dependent lung cancer cells.
Disease, Cell line, Treatment
View SamplesDetermination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Specimen part
View SamplesDetermination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Specimen part
View SamplesEvolutionary conserved biological rhythms play a fundamental role in the physiology and behavior of all light-sensitive organisms. Generation of rhythmic expression of clock-controlled genes is orchestrated by a molecular circadian clock constitutes by interconnected negative feedback loops of transcription factors. In this study, we want to characterize gene which also present a rhythmic translation through the characterization of genes with a rhythmic polysomal/total RNA ratio.
The circadian clock coordinates ribosome biogenesis.
Sex, Age, Specimen part, Disease, Time
View SamplesTime series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision.
Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.
Subject
View SamplesThe behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Gene expression, molecular class changes, and pathway analysis after neoadjuvant systemic therapy for breast cancer.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor).
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer.
Specimen part
View Samples