Murine Runx3 is expressed in developing bone osteoblasts (OBLs) and its deletion in these cells culminates in severe congenital osteopenia. We demonstrate that Runx3 is non-redundantly involved in the proliferation of early pre-committed OBL progenitor cells, a critical step in the generation of adequate numbers of bone-forming OBLs. Thus, in the absence of Runx3 in cells of this lineage, the number of mature/active OBLs is significantly diminished, providing a mechanistic explanation to the observed osteopenia.
Loss of osteoblast Runx3 produces severe congenital osteopenia.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
Sex, Age, Specimen part
View SamplesCD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
Sex, Age
View SamplesEsam/CD4+ dendritic cells are part of the innate immunity essential for priming and activating of CD4+ T cells
Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sex, Specimen part, Cell line
View SamplesRUNX3 is one of three mammalian Runt-domain transcription factors that regulate gene expression in several types of immune cells. Runx3-deficiency in mice is associated with a multitude of defects in the adaptive and innate immunity systems, including the development of early onset colitis. Our study reveals that conditional deletion of Runx3 specifically in mononuclear phagocytes (MNP) recapitulates the early onset spontaneous colitis seen in Runx3-/- mice. We show that Runx3 is expressed in colonic MNP, including RM and the dendritic cell cDC2 subsets and its loss results in impaired differentiation/maturation of both cell types.
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sex, Specimen part
View Samplescharacterize the molecular signature of PB-IMC in different stages of tumor development, thus possibly leading to a novel, sensitive and elegant approach for early cancer detection and surveillance. Overall design: Two types of cancer. For each type 4 groups (day 0, day 4, day 8, day 11), for each group 3 biological repeats
The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.
Specimen part, Cell line, Subject
View SamplesWe report the effect of DKK1 treatment during culture on the length and transcriptome of embryos on day 15 of development, supporting the notion that changes early in development affect later stages of development. Overall design: Bovine embryos were produced in vitro and exposed to either 0 or 100 ng/ml DKK1 from day 5 to 7 of culture. Embryos were transferred on day 7 and recovered on day 15 for evaluation of length and transciptome
Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation.
Treatment, Subject
View SamplesBackground & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy.
UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation.
Specimen part, Cell line
View SamplesBy using high-density DNA microarrays, we analyzed the gene-expression profile in a panel of germ cell tumour cell lines
Differentiation-Dependent Regulation of Human Endogenous Retrovirus K Sequences and Neighboring Genes in Germ Cell Tumor Cells.
Specimen part, Cell line
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