When misexpressed in late Drosophila prepupae, the transcription factor Senseless (Sens) blocks death of the larval salivary glands that normally occurs in the early pupa. The aim of the experiment was to identify genes responding to Sens that might mediate the effect of the protein on cell death and other biological processes. The yeast transcription factor GAL4, expressed from a heat-inducible transgene (P{GAL4-Hsp70.PB}89-2-1), was used to drive expression of Sens from a UAS-sens transgene. After crossing the GAL4 and UAS lines, expression of GAL4 was induced by a 30-min heat shock treatment (37 C) of the progeny at 9 hours after puparium formation. Salivary glands were dissected at 14 hours after puparium formation and RNA isolated for microarray analysis with Affymetrix GeneChips. Control samples were obtained from animals treated the same way carrying one copy of the GAL4 transgene (progeny of a cross between flies of the P{GAL4-Hsp70.PB}89-2-1 and w1118 strains) and w1118 animals. The microarray data identified several genes associated with programmed cell death, including caspase genes, which respond to Sens. In addition, the data show that many Drosophila genes respond to the yeast transcription factor GAL4 in a UAS-independent manner. To identify target genes of Sens that are of biological relevance, gene expression patterns in the presence of Sens were compared to gene expression patterns in both the presence and the absence of GAL4. This comparison revealed that Sens seems to preferentially downregulate targets that are upregulated by GAL4, suggesting that these genes may not necessarily constitute true transcriptional targets of Sens.
A genomic response to the yeast transcription factor GAL4 in Drosophila.
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View SamplesWhen misexpressed in late Drosophila prepupae, the transcription factor Fork head (Fkh) blocks death of the larval salivary glands that normally occurs in the early pupa. The aim of the experiment was to identify genes responding to Fkh that might mediate the effect of the protein on cell death and other biological processes. Fkh was expressed in the line P[hs-Fkh111] from a heat-inducible transgene that encodes wild-type Fkh protein. Expression of Fkh was induced by incubating prepupae for 30 min in a 37 C water bath, starting at 9.5 hours after puparium formation. Salivary glands were dissected at 14 hours after puparium formation and RNA isolated for microarray analysis with Affymetrix GeneChips. Control samples were obtained from w1118 animals treated the same way. The microarray analysis identified 55 genes annotated as functioning in apoptosis whose expression was at least 1.5-fold changed by Fkh. These genes include the death genes hid and reaper, which play a central role in the control of salivary gland death. Other groups of significantly enriched genes include genes functioning in autophagy, steroid-signaling pathways, salivary gland secretion, and phospholipid metabolism. In addition, the microarray data identify genes as responsive to Fkh that are known to be controlled by the FOXA counterparts of Fkh in vertebrates, indicating that target genes and biological processes controlled by Fkh are evolutionarily conserved.
Genes and biological processes controlled by the Drosophila FOXA orthologue Fork head.
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View SamplesWe performed RNAseq on l(3)mbt mutant somatic ovaries to gain a genome-wide view of tissue-specific gene expression changes in L(3)mbt-depleted somatic ovaries. Overall design: Examination of gene expression changes in mutant and control somatic ovaries.
L(3)mbt and the LINT complex safeguard cellular identity in the <i>Drosophila</i> ovary.
Specimen part, Subject
View SamplesBehavioral analysis confirmed that the 14-day social defeat sessions resulted in induction of depressive-like states measured in social interaction and light/dark tests. The combined data show that stress-induced depressive states are associated with molecular and structural changes that demyelinate the prefrontal cortex.
Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.
Specimen part
View SamplesWe have generated tumorigenic (S2N) and non-tumorigenic (S2), normal-like to basal-like breast cancer cell lines from primary tumors. At high in vivo inoculation cell numbers of 10^6 cells/mouse both S2N and S2 monolayer as well as sphere culture cells grew at similar rates. However, at low inoculation cell numbers down to 10^3 cells only S2N sphere cells generated xenograft tumors. mRNA profiling revealed a unique cluster pattern of the tumorigenic S2N sphere cells, but a detailed analysis of TIC relevant transcription factors like Oct3, Sox and Nanog family members, Myc, Slug or Twist1 revealed no consistently increased expression in the highly tumorigenic cell lines. Our data indicate that the intrinsic genetic and functional markers investigated are not solely indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells.
Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells.
Disease, Cell line
View SamplesAn animals ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brains immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglial RNAs were isolated and analyzed by global gene expression microarrays. Microglia transcriptome from CSD-S mice was enriched for pathways that describe phases of CNS healing to sterile injury including, inflammation, oxidative stress, debris clearance, and wound resolution. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or HC mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by leakage of blood-born substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.
Specimen part
View SamplesIPH-926 is an anticancer drug-resistant tumor cell line derived from a chemo-refractory human infiltrating lobular breast cancer (ILBC). IPH-926 ILBC cells were subjected to gene expression profiling using an Affymetrix HG U133 Plus 2.0 array.
ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells.
Specimen part, Cell line
View SamplesThe purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs).
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Specimen part, Disease, Disease stage
View SamplesThe purpose of this study was to identify molecular markers of pathologic response to neoadjuvant dose-dense docetaxel treatment using gene expression profiling on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with 75 mg/m2 IV of docetaxel on day 1 of each cycle every 2 weeks x 4 cycles . Tumor tissue from pretreatment biopsies was obtained from 12 patients enrolled in the study. Gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR).
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Specimen part, Treatment
View SamplesNGS from RNA-seq of triple-negative breast cancer cell lines under standard growth conditions were obtained to identify transcriptional features associated with individual triple-negative breast cancer subtypes. All lines identified have been authenticated by short-tandem repeat sequencing and tested to be negative for mycoplasma.
Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.
Sex, Specimen part, Disease, Cell line
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