Abstract Two major dendritic cell (DC) subsets have been described in the islets of mice: The immunogenic CD8-CD11b+ DCs and the tolerogenic CD8+CD103+ DCs. We have recently reported on reduced numbers of the minor population of tolerogenic CD8+CD103+ DCs in the pancreas of 5 week old pre-diabetic non-obese diabetic (NOD) mice. Aim: To analyze also the larger subset of CD11c+CD8- DCs isolated from the pancreas of pre-diabetic NOD mice 1) for maturation and tolerance inducing molecules found abnormally expressed on CD8+CD103+ DCs, and 2) for genome-wide gene expression to further elucidate abnormalities in underlying gene expression networks. Methods: CD11c+CD8- DCs were isolated from 5 week old C57BL/6 and NOD pancreas. Expression of cell surface markers including CD86, CCR5, CD11b, CD103, Clec9a, CD24 and CD200R3 were measured by FACS. Genome-wide gene expression by microarray was assessed during the steady state and after in vitro LPS stimulation. Results: The steady state pancreatic CD11c+ CD8- DCs during the pre-diabetic stage showed: 1) A reduced expression of several gene networks important for the prime functions of the cell, such as for cell renewal, immune stimulation and immune tolerance induction, for migration and for the provision of growth factors for beta cell regeneration. This general deficiency state was corroborated by a reduced in vivo proliferation (BrdU incorporation) of the cells and the reduced expression in FACS analysis of CD86, CCR5, CD103, Clec9a, CD24 and CD200R3 on the cells. 2) A hyper reactivity of these cells to LPS correlated with an enhanced pro-inflammatory state characterized by altered expression of a number of classical pro-inflammatory factors and cytokines. Conclusion: The NOD CD11c+CD8- DCs seem to be Janus-faced depending on the conditions: Deficient in steady state with reduced immune stimulation capabilities also for tolerance induction; over-inflammatory with a molecular profile suggesting a preferential stimulatory capacity for Th1 cells when encountering a Pathogen-Associated Molecular Pattern (PAMP) in the form of LPS.
The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
Sex, Age, Specimen part, Treatment
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to imidazolinone (Arsenal) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to primisulfuron (Beacon) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to sulfometuron methyl (oust XP) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to triazolopyrimidine (FirstRate) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesThe mammalian circadian clock system is made up of individual cell and tissue clocks that function as a coherent network, however it remains unclear which rhythmic functions of the liver clock are autonomous or rely on clocks in other tissues. Here, using mice which only have a functioning liver clock, we investigate the autonomous vs non-autonomous reatures of the liver clock and diurnal rhythmicity in the liver Overall design: 8-12 week-old, female WT, KO and Liver-RE BMAL1-stop-FL mice (see referenced paper for details) were fed ad libitum normal chow under 12hr light/ 12hr dark schedule. Livers were harvested every 4 hours over the circadian cycle at ZT0, 4, 8, 12, 16, 20 (n=3 per time point per group). Total RNA was extracted and used for RNA-seq.
Defining the Independence of the Liver Circadian Clock.
Specimen part, Subject
View SamplesOur earlier study demonstrated that when CFSE-labeled LCMV-or Pichinde virus-immune spleen leukocytes were transferred into T cell-deficient hosts, the bona fide virus-specific memory cells underwent relatively limited cell division and were substantially diluted in frequency by other more extensively proliferating cells originating from that donor cell population. We questioned how the slowly dividing population, which contained bona fide memory cells, differed from the rapidly dividing cells, which contained memory-like cells. As a preliminary screen we performed a comparative genome-wide microarray analysis of genes expressed on sorted rapidly proliferating (CFSE-low) and slowly proliferating (CFSE-high) CD8 cell populations
Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation.
Age, Specimen part
View SamplesComparison of rosette leaves of two different RAP2.2 overexpressing lines with wild type leaves. The AP2/EREBP transcription factor RAP2.2 was shown to bind to a cis-acting motif within the phytoene synthase promoter from Arabidopsis. To investigate effects of increased RAP2.2 levels, two RAP2.2 overexpressing Arabidopsis thaliana (ecotype Wassilewskija) lines were generated: one line, nosr2, carried the nos promoter and showed a two-fold increase in RAP2.2 transcript level, the second line, cmr-5, carried four copies of the CaMV-35S enhancer and showed a 12-fold increase. However, neither weak nor strong increase in RAP2.2 transcript amounts had any effect on RAP2.2 protein levels as shown by Western blot analysis. The strong robustness of RAP2.2 protein levels towards transcriptional changes can be explained by specific protein degradation which includes SINAT2, an E3 ubiquitin ligase which was isolated using a two-hybrid approach. Accordingly, global gene expression analysis using both RAP2.2 overexpressing lines showed only minor transcriptional changes which are probably due to minor growth variation than to mechanisms involved in the down-regulation of RAP2.2 protein amounts.
Transcription factor RAP2.2 and its interacting partner SINAT2: stable elements in the carotenogenesis of Arabidopsis leaves.
Specimen part
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 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
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