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 SamplesOur study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)). Overall design: Lungs were harvested from neutrophil-depleted (antibody or DT) or non-depleted mice, in normal light-controlled mouse facility (ZT4) or 12h inverted light cabinets (ZT16). Experiments were carried out over 3 batches (July 2017, September 2017, and April 2018), with 3 or 4 mice per group. Antibody-depleted and non-depleted mice were tested for the July 2017 and September 2017 batches, whereas DT-depleted mice were tested only in April 2018.
Neutrophils instruct homeostatic and pathological states in naive tissues.
Specimen part, Treatment, Subject
View SamplesOur study aims to analyze time-dependent changes in neutrophil phenotype, compare them with included neutrophil-specific mutants, and indentify common signatures among the 5 groups Overall design: Blood neutrophils from wild-type and mutants were isolated based on Ly6G staining, then standard RNA extraction procedures were performed. Wild-type samples were extracted at ZT5 and ZT13, all other samples at ZT5.
A Neutrophil Timer Coordinates Immune Defense and Vascular Protection.
Sex, Specimen part, Cell line, Subject
View SamplesOur study aims to analyze time-dependent changes in neutrophil phenotype Overall design: Blood neutrophils were isolated based on Ly6G staining, then standard RNA extraction procedures were performed. This samples were extracted at ZT13.
A Neutrophil Timer Coordinates Immune Defense and Vascular Protection.
Specimen part, Subject
View SamplesInvestigating neuronal and photoreceptor regeneration in the retina of zebrafish has begun to yield insights into both the cellular and molecular means by which this lower vertebrate is able to repair its central nervous system. However, knowledge about the signaling molecules in the local microenvironment of a retinal injury and the transcriptional events they activate during neuronal death and regeneration is still lacking. To identify genes involved in photoreceptor regeneration, we combined light-induced photoreceptor lesions, laser-capture microdissection (LCM) of the outer nuclear layer (ONL) and analysis of gene expression to characterize transcriptional changes for cells in the ONL as photoreceptors die and are regenerated. Using this approach, we were able to characterize aspects of the molecular signature of injured and dying photoreceptors, cone photoreceptor progenitors and microglia within the ONL. We validated changes in gene expression and characterized the cellular expression for three novel, extracellular signaling molecules that we hypothesize are involved in regulating regenerative events in the retina.
Identification of the molecular signatures integral to regenerating photoreceptors in the retina of the zebra fish.
No sample metadata fields
View SamplesNeural stem cells (NSC) derived from human parthenogenic stem cells (hpSC) have been observed to show stronger positive functional effects than hpSC-derived dopaminergic neuron precursors (DAP) in treatment of induced Parkinson Disease in animal models. RNAseq of the two types of cells were normalized and analyzed to compare gene expression profiles. Overall design: cDNA library of hpsC, NSC and DAP triplicates were sequenced using Illumina HiSeq 2000. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.
Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson's disease.
No sample metadata fields
View SamplesInadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials.
The skeletal muscle transcript profile reflects accommodative responses to inadequate protein intake in younger and older males.
Sex
View SamplesThe hormone prolactin is implicated in the pathogenesis of breast cancer, and a subset of prolactin-induced gene expression is mediated by CypA activity.
Inhibition of the Activity of Cyclophilin A Impedes Prolactin Receptor-Mediated Signaling, Mammary Tumorigenesis, and Metastases.
Sex, Specimen part, Disease, Disease stage, Cell line
View SamplesStudying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established.
Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.
Sex, Age, Specimen part
View Samples