The classical concept of bone marrow-derived mesenchymal stem cells (BM-MSC), intended as a uniform, broad potent population, is progressively being substituted by the idea that the bone marrow harbors heterogeneous populations of non-hematopoietic stem cells. This in vivo heterogeneity is also amplified by the different experimental strategies used to isolate/culture them. Among the exogenous factors described to affect MSC in vitro growth, basic-fibroblast growth factor (bFGF) is one of the most common growth factors used to expand stem cells. Moreover, it has been reported that its signaling is associated with the mainteinance of stemness of a variety of stem cells, included MSC. Using an ectopic model of bone regeneration, we have previously described that the implantation of cells with different commitment levels, differentially influences the capacity to recruit host cells, activating endogenous regenerative mechanisms. Due to its properties, we here demonstrate that the addition of bFGF to primary BM cultures, leads to the selection of specific subpopulations able to induce a different host regenerative response, when in vivo implanted in association with suitable ceramic scaffolds. Moreover, taking advantage of a multiparametric and comparative genomic and proteomic approach, it has been evaluated how different culture conditions combine to bring about appreciable changes in the secretome of the cells, that consequently influence their in vivo regenerative behaviour. The full comprehension of the regulatory mechanisms that rule the host response depending on the type and differentiative stage of the transplanted cells could help us to develop novel clinical strategies where host cells could directly contribute to regenerate the appropriate tissue.
The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model.
Specimen part, Disease
View SamplesThere is differential expression of genes between cases and controls using microarray analysis, and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection.
Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.
Specimen part, Disease, Disease stage
View SamplesWe studied the transcriptional profile in yeast cells in response to heterologous expression of mammalian activated AKT1
Heterologous mammalian Akt disrupts plasma membrane homeostasis by taking over TORC2 signaling in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe studied the transcriptional profile in response to acute PtdIns-4,5P2 depletion induced by heterologous expression of a plasma membrane-directed version of mammalian PI3K catalytic subunit (p110-CAAX).
The yeast cell wall integrity pathway signals from recycling endosomes upon elimination of phosphatidylinositol (4,5)-bisphosphate by mammalian phosphatidylinositol 3-kinase.
No sample metadata fields
View SamplesThe rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sex, Specimen part, Treatment, Subject
View SamplesWe hypothesize that germline variation influences susceptibility to aggressive prostate tumor
A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Disease, Cell line
View SamplesAnalysis of gene expression levels in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Cell line
View SamplesPurpose: Citron kinase (CitK) knockout mice show a severe form of primary microcephaly, associated with ataxia and lethal epilepsy. This phenotype is caused by massive apoptosis occuring during embryonic and post-natal brain development, associated with cytokinesis failure. Cerebellum is the tissue showing highest sensitivity to CitK loss. The clinical phenotype of CitK knockout mice is significantly resued by P53 inactivation. In addition, CitK/P53 double knockout brains have almost normal levels of apoptosis, but display high percentage of binucleated and multinucleated cells. The aim of this study was to analyze the gene expression changes produced in developing neural tissue by CitK loss and to determine which alterations are P53-dependent. expression changes Methods: We analyzed by RNA sequencing total RNA extracted from P4 cerebellum of mice characterized by the following genotypes: 1. CitK +/-, P53 +/- (CTRL); 2. CitK -/-, P53 +/- (CitK-KO); 3. CitK +/-, P53 -/- (P53-KO); 4. CitK -/-, P53 -/- (D-KO). Biological triplicates were analyzed per every genotype. Conclusions: The loss of CitK leads to a strong reduction of the expression of pro-neural genes and induces a P53-related pro-apoptotic gene sets. The analysis of D-KO mice reveals that most of these changes are P53-dependent, but many genes implicated in growth arrest are induced through P53-independent mechanisms. Overall design: Cerebellar mRNA profiles of 4-day old mice of CTRL, CitK-KO, P53-KO and D-KO mice were generated by deep sequencing, in triplicate, using Illumina HiScan SQ
ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.
Specimen part, Cell line, Subject
View SamplesThe transcriptome of the three atino80 allelic mutants was compared to that of wild-type and 50B Arabidopsis plants (see Fritsch et al. 2004). Since the transcriptomes of 50B and wild-type plants were found to be identical, we compared expression in the mutant with 50B and with wild-type without distinction. Therefore, we had four replicates of the wild type condition (50B line, wild-type) and two replicates for each of the mutant alleles (atino80-1, atino80-2 and atino80-3), all ecotype Columbia. All lines were profiled in duplicate (grown independently at 2-week-intervals).
The INO80 protein controls homologous recombination in Arabidopsis thaliana.
Age, Specimen part
View Samples