Osteosarcoma patients with development of pulmonary metastasis have still poorer prognosis in spite of aggressive treatment. However, molecular mechanism of metastasis is still unknown.
Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma.
Sex, Age
View SamplesOur previous investigation indicated that high-virulence C. gattii (C. gattii TIMM 4097) tend to reside in the alveoli, whereas low-virulence C. gattii (C. gattii TIMM 4903) tend to be washed out from the alveoli and move into the central side of the respiratory system. To test this hypothesis, we performed microarray assay.
How histopathology can contribute to an understanding of defense mechanisms against cryptococci.
Sex, Specimen part
View SamplesThe human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
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View SamplesOncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS.
BRD7 is a candidate tumour suppressor gene required for p53 function.
Specimen part, Disease, Cell line
View SamplesDespite widespread use of sunscreens that minimize erythema by blocking ultraviolet B (UVB) radiation, incidence rates of melanoma continue to rise. In considering this disparity between intervention and disease prevalence, we investigated the in vivo transcriptome of human skin treated with sunscreen and solar-simulated radiation (ssR). A focal skin area of healthy participants was exposed to ssR at 1 minimal erythema dose (MED), 0.1 MED or 100 J/m2 with or without prior application of sunscreen, or to non-UVB-spectrum of ssR (solar-simulated UVA/visible/infrared radiation: ssA). Skin biopsies were analyzed using expression microarrays.
Transcriptional signatures of full-spectrum and non-UVB-spectrum solar irradiation in human skin.
Sex, Specimen part
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
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