Ionizing radiation (IR) has long been associated with reduced hematopoietic function and increased malignancies, although the mechanisms behind this relationship remain poorly understood. The carcinogenic effect of IR has been commonly attributed to the direct induction of DNA damage. We demonstrate that IR exposure results in long-term, somatically heritable, cell-intrinsic reductions in HSC self-renewal that is mediated by C/EBPa and reversed by Notch, both of which are associated with human leukemias. Remarkably, restoration of HSC self-renewal prevents selection for C/EBPa loss of function in previously irradiated HSC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal to prevent damaged HSC from contributing to hematopoiesis. This "programmed mediocrity" is advantageous for the localized insults animals have evolved to deal with, but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations Overall design: Examination of mRNA levels in in vitro and in vivo Hematopoietic Stem Cell that exposed to IR Ionizing radiation (IR) or control. Each group has three replicates.
Contrasting roles for C/EBPα and Notch in irradiation-induced multipotent hematopoietic progenitor cell defects.
No sample metadata fields
View SamplesInadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials.
The skeletal muscle transcript profile reflects accommodative responses to inadequate protein intake in younger and older males.
Sex
View SamplesBackground: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown.
1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1.
Specimen part, Cell line, Treatment, Time
View SamplesInadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle mRNA levels.
Inadequate protein intake affects skeletal muscle transcript profiles in older humans.
Sex
View SamplesThis is an analysis of Caco-2 BBe cell spontaneous differentiation. JF2dR1-JF2dR4 = proliferating cells; JF8dR1-JF8dR4 = 4 d post-confluent; JF15dR1-JF15dR4 = 11 d pc, differentiated
Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesCell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Specimen part, Cell line
View SamplesAffymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
Specimen part, Cell line
View SamplesA major goal in prostate stem cell biology is to identify genes, pathways, or networks that control self-renewal and multilineage differentiation. We hypothesize that 1,25 dihydroxyvitamin D3 can induce differentiation of prostatic progenitor/stem cells, thus serving as an in vitro model with which to study the molecular mechanisms of stem cell differentiation by 1,25 dihydroxyvitamin D3. 1,25 dihydroxyvitamin D3 elicits its effects primarily through transcriptional regulation of genes, so microarray studies were used to gain insight into the cellular response to 1,25 dihydroxyvitamin D3.
Interleukin-1α mediates the antiproliferative effects of 1,25-dihydroxyvitamin D3 in prostate progenitor/stem cells.
Specimen part
View SamplesWe assayed the effect of c-Jun overexpression on gene expression in the three DDLPS cell lines using RNA-Seq (Illumina). Overall design: 141, LPS12 and 510 has been overexpressed with c-Jun or control c-DNA and results were analyzed in high-througput sequencing metadata.
c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas.
No sample metadata fields
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