AML1-ETO expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of an early self-renewing primitive progenitor cell with multilineage potential and stem cell ability, but these cells do not induce leukemia in immunodeficient mice. This comparative microarray study was initiated to determine the differences in the transcriptome of AML-ETO-expressing CD34+ cells after extended culture in vitro, using normal cord blood cells expanded for 6-8 weeks in vitro and subsequently purified for the CD34+ population as the control comparison.
p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death.
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View SamplesMicroarray analysis of purified pachytene spermatocytes and round spermatids. Each stage was examined in wild type and RNF8 knockout mice in two biological replicates.
RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids.
Specimen part
View SamplesRNA-seq was performed using Thy1- and c-Kit+ spermatogonia from 7-days-old PRC1ctrl or dKO mice. Overall design: Duplicate RNA-seq analyses using spermatogonia from 7-days-old PRC1ctrl or dKO mice
Polycomb directs timely activation of germline genes in spermatogenesis.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Specimen part, Cell line
View SamplesEstrogen receptor (ER) is a key regulator of breast growth and breast cancer development. However, the role of ER in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ER with estrogen induced transcript and metabolic profiling, we demonstrate that ER reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ER target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ER promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ER for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ER target CHPT1 in breast cancer supports its potential as a therapeutic target.
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Age, Specimen part, Disease
View SamplesLiver global gene expression patterns of 9 GNMT-knockout mice histopathologically determined to have non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) together with 10 MAT1A-knockout mice histopathologically determined to have steatosis and NASH. All these have their respective wild type patterns. These were analyzed to define signatures to study the pathogenesis of NAFLD-derived HCC, explore which subtypes of cancers can be investigated using mouse models and define a signature of HCC differential survival that can be used to characterize HCC subtypes of different survival derived from mixed etiologies.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Age, Specimen part, Disease
View SamplesGlobal gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Specimen part, Disease
View SamplesLiver global gene expression patterns of 15-month-old MAT1A knockout mice histopathologically determined to have hepatocellular carcinoma (HCC). 5 samples are of tumoral tissue and 5 samples are of peritumoral tissue. All these have their respective wild type patterns. These were analyzed to define signatures to study the pathogenesis of NAFLD-derived HCC, explore which subtypes of cancers can be investigated using mouse models and define a signature of HCC differential survival that can be used to characterize HCC subtypes of different survival derived from mixed etiologies.
Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
Age, Specimen part, Disease
View SamplesAdult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.
Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.
Sex, Time
View Samples