Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.
Articular cartilage regeneration by activated skeletal stem cells.
Specimen part, Treatment
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesCognitive decline is a common occurrence of the natural aging process in animals, and studying age-related changes in gene expression in the brain might shed light on disrupted molecular pathways that play a role in this decline. The fruit fly is a useful neurobiological model for studying aging due to its short generational time and relatively small brain size. We investigated age-dependent changes in the Drosophila melanogaster whole-brain transcriptome by comparing 5-, 20-, 30- and 40-day-old flies of both sexes. We used RNA-Sequencing of dissected brain samples followed by differential expression, temporal clustering, co-expression network and gene ontology enrichment analyses. Our study provides the first transcriptome profile of aging brains from fruit flies of both sexes, and it will serve as an important resource for those who study aging and cognitive decline in this model. Overall design: 24 biological sample replicates (3 per age per sex), each consisting of pooled dissected whole-brains from 18 flies, were processed for total RNA extraction and sequencing. Age groups were 5, 20, 30 and 40 days old. One sample from the 30-day-old male group had to be removed from analysis due to sample contamination.
Brain transcriptome changes in the aging Drosophila melanogaster accompany olfactory memory performance deficits.
Sex, Age, Specimen part, Cell line, Subject
View SamplesGene expression profiling was performed on CNS tissue from neonatal mice carrying the T9H translocation and maternal or paternal duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the PWS/AS locus. The transcripts were termed Pec2 and Pec3 for paternally expressed in the CNS.Our analysis also revealed imprinting of Magel2, Mkrn3, Ndn,Ube3a and Usp29, as well as Pec2 and Pec3 in embryonic brain, 15.5 dpc, and provided a survery of biallelically expressed genes on proximal Chromosomes 7 and 15 in embryonic and neonatal CNS.
Novel paternally expressed intergenic transcripts at the mouse Prader-Willi/Angelman Syndrome locus.
No sample metadata fields
View SamplesGiven the increased T cell mediated DTH response to Candida albicans in female compared to male mice, we asked whether female and male lymphnodes differed in their expression of genes relevant to cell recruitment. Overall design: Pooled Lymph Nodes of C57Bl/6 Wild-type Female N=6, Wild-type Male N=6, or C57Bl/6 Four Core Genotype XY Male N=3 mice were analyzed by RNAseq for differences in gene expression.
Sex Differences in Mouse Popliteal Lymph Nodes.
Age, Cell line, Subject
View SamplesGene expression profiling was performed on CNS tissue from neonatal mice carrying the T9H translocation and maternal or paternal duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the PWS/AS locus. The transcripts were termed Pec2 and Pec3 for paternally expressed in the CNS.Our analysis also revealed imprinting of Magel2, Mkrn3, Ndn,Ube3a and Usp29, as well as Pec2 and Pec3 in embryonic brain, 15.5 dpc, and provided a survery of biallelically expressed genes on proximal Chromosomes 7 and 15 in embryonic and neonatal CNS.
Novel paternally expressed intergenic transcripts at the mouse Prader-Willi/Angelman Syndrome locus.
No sample metadata fields
View SamplesGene expression profiling was performed on CNS tissue from neonatal mice carrying the T9H translocation and maternal or paternal duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the PWS/AS locus. The transcripts were termed Pec2 and Pec3 for paternally expressed in the CNS.Our analysis also revealed imprinting of Magel2, Mkrn3, Ndn,Ube3a and Usp29, as well as Pec2 and Pec3 in embryonic brain, 15.5 dpc, and provided a survery of biallelically expressed genes on proximal Chromosomes 7 and 15 in embryonic and neonatal CNS.
Novel paternally expressed intergenic transcripts at the mouse Prader-Willi/Angelman Syndrome locus.
No sample metadata fields
View SamplesGene expression was compared between E18.5 Gata4Gata6 double conditional knockout (cKO) small intestinal epithelium and E18.5 control mouse small intestinal epithleium.
GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development.
Specimen part
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