To realize the full potential of human embryonic stem cells (hESC), it is important to develop culture conditions that maintain hESC in a pluripotent, undifferentiated state. A low O2 atmosphere (~4% O2), for example, prevents spontaneous differentiation and supports self-renewal of hESC. To identify genes whose expression is sensitive to O2 conditions, microarray analysis was performed on RNA from hESC that had been maintained under either 4% or 20% O2. Of 149 genes differentially expressed, 42 were up-regulated and 107 down-regulated under 20% O2. Several of the down-regulated genes are most likely under the control of hypoxia-inducing factors and include genes encoding enzymes involved in carbohydrate catabolism and cellular redox state. Although genes associated with pluripotency, including OCT4, SOX2 and NANOG were generally unaffected, some genes controlled by these transcription factors, including LEFTY2, showed lowered expression under 20% O2, while a few genes implicated in lineage specification were up-regulated. Although the differences between O2 conditions were generally subtle, they were observed in two different hESC lines and at different passage numbers. The data are consistent with the hypothesis that 4% O2 favors the molecular mechanisms required for the maintenance of pluripotency.
Identification of oxygen-sensitive transcriptional programs in human embryonic stem cells.
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View SamplesAnalysis of kidneys from 12 week BPH/2J hypertensive and age matched normotensive BPN/3J controls - males and females. The results provide insights into the genes that are involved in hypertension in both males and females, as well as highlight mechanisms that underlye sex differences in hypertension.
Identification of genes with altered expression in male and female Schlager hypertensive mice.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWe used microarrays to detail the global gene expression changes during aging in fly heads and identified genes related to the unfolded protein response are up-regulated upon aging.
EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila.
Age, Specimen part
View SamplesCellular senescence is an irreversible proliferative arrest and can be triggered in many cell types in response to diverse forms of cellular damage or stress.
Senescence of activated stellate cells limits liver fibrosis.
No sample metadata fields
View SamplesAbout 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesGenome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Overall design: Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).
Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.
No sample metadata fields
View SamplesAlternative RNA splicing analysis in Hep3B cell cultured under 21% (N1,3,5) or 1.2% (H2,4,6) oxygen
Hypoxia regulates alternative splicing of HIF and non-HIF target genes.
Cell line
View SamplesEndometriosis is a benign gynecological condition that causes significant morbidity due to reduced fertility, pelvic pain and inflammatory dysfunctions. High-fat dietary intake has been linked to higher systemic inflammation and oxidative stress, which are both features of women with endometriosis. We evaluated the effects of high-fat diet (HFD) on endometriosis progression using immunocompetent mouse model wherein ectopic lesion was induced in wildtype and kruppel-like factor 9 (KLF9)- null donor mice. Results showed that HFD leads to increased ectopic lesion numbers and higher body weight gain. The HFD-promotion of lesion establishment was associated with decreased stromal estrogen receptor 1 and progesterone receptor expression, increased macrophage infiltration, and enhanced expression of pro-inflammarory and pro-oxidative stress pathway genes. Further, lesion-bearing mice had higher peritoneal fluid TNF- and elevated local/systemic redox status than control-fed mice.
High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.
Specimen part
View SamplesMaintenance and propagation of breast cancer stem cells (BCSCs) is mediated via cytokine and growth factor networks. Direct in vivo linkage between dietary regulation of mammary stem (MaSC)/progenitor cell numbers and protection from breast cancer has not been reported. Here, we investigated the effect of post-weaning intake of soy protein isolate (SPI) relative to the control casein (CAS) diet on the stem/progenitor population and tumor formation in MMTV-Wnt1-Transgenic (Wnt1-Tg) female mice. Gene expression profile of the basal (MaSC-enriched) sub-population in preneoplastic Wnt1-Tg mice demonstrated a stem cell-like expression pattern and markedly suppressed expression of inflammatory cytokines, C-X-C family chemokines, and metastasis-associated genes with dietary SPI exposure.
Dietary suppression of the mammary CD29(hi)CD24(+) epithelial subpopulation and its cytokine/chemokine transcriptional signatures modifies mammary tumor risk in MMTV-Wnt1 transgenic mice.
Specimen part
View SamplesA conserved molecular pathway has emerged controlling endoderm formation in Xenopus zebrafish and mice. Key genes in this pathway include Nodal ligands and transcription factors of the Mix-like paired homeodomain class, Gata4-6 zinc finger factors and Sox17 HMG domain proteins. While a linear epistatic pathway has been proposed, the precise hierarchical relationships between these factors and their downstream targets are largely unresolved. Here we used a combination of microarray analysis and loss-of-function experiments to examine the global regulatory network controlling Xenopus endoderm formation. We identified over 300 transcripts enriched in the gastrula endoderm, including most of the known endoderm regulators as well as over a hundred uncharacterized genes. Surprisingly only 10% of the endoderm transcriptome is regulated as predicted by the current linear model. We find that Nodals, Mixer and Sox17 have both shared and distinct sets of downstream targets and that a number of unexpected autoregulatory loops exist between Sox17 and Gata4-6, Sox17 and Bix1, 2, 4 and between Sox17 and Xnr4. We find that Mixer does not function primarily via Sox17 as previously proposed. This data provides a new insight into the complexity of endoderm formation and will serve as valuable resource for establishing a complete endoderm gene regulatory network.
Global analysis of the transcriptional network controlling Xenopus endoderm formation.
No sample metadata fields
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