Using cell-restricted transcriptome analysis, here we show that Drosophila ommatidial cone (or Semper) cells are enriched for conserved glial regulators and effectors, including many characteristic of vertebrate retinal glia: Müller glia and astrocytes. Overall design: RNA-seq based analysis of Drosophila retinal cone cells (3 developmental stages) and photoreceptors. 1 sample per cell type - 4 total libraries sequenced.
Multifunctional glial support by Semper cells in the Drosophila retina.
Specimen part, Subject
View SamplesMesenchymal stromal cells (MSC) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival and differentiation of hematopoietic stem/progenitor cells (HSPC) in the stem cell niche. MSC are functionally and phenotypically altered in myelodysplastic syndromes (MDS), contributing to disease progression. MDS MSC do not harbor recurrent genetic alterations but have been shown to exhibit an altered methylome compared to MSC from healthy controls. We examined growth, differentiation and HSPC-supporting capacity of ex vivo expanded MSC from MDS patients in comparison to age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). We show that AZA exerts a direct effect on MSC by modulating their differentiation potential. Osteogenesis was significantly boosted in healthy MSC while adipogenesis was inhibited in both healthy and MDS MSC. In co-culture experiments, both AZA treated MDS MSC and healthy MSC exhibited enhanced support of non-clonal HSPC which was associated with increased cell cycle induction. Conversely, clonal MDS HSPC were inhibited by contact with AZA treated MSC. RNA-sequencing analyses of stromal cells revealed changes in pathways essential for HSPC support as well as in immune regulatory pathways. In sum, our data demonstrate that AZA treatment of stromal cells leads to upregulation of HSPC-supportive genes and cell cycle induction in co-cultured healthy HSPC, resulting in a proliferative advantage over clonal HSPC. Thus, restoration of functional hematopoiesis by AZA may be driven by activated stromal support factors in MSC providing cell cycle cues to healthy HSPC. Overall design: RNA sequencing was performed on a mesenchymal stromal cell line (EL08-1D2), either untreated or treated with Azacitidine [(-)AZA vs. (+)AZA].
Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis.
Treatment, Subject
View SamplesThis study aims at a comprehensive understanding of the genomic program activated during early-phase of collateral vessel growth in a rat model for cerebral adaptive arteriogenesis (3-VO). While arteriogenesis constitutes a promising therapeutic concept for cerebrovascular ischemia, genomic profiles essential for therapeutic target identification were analysed solely for collateral arteries of the heart and periphery. Despite challenging anatomical conditions of the brain the 3-VO model allows identification of differentially expressed genes during adaptive cerebral arteriogenesis by selective removal of the posterior cerebral artery (PCA).
Induction of cerebral arteriogenesis leads to early-phase expression of protease inhibitors in growing collaterals of the brain.
Age
View SamplesWe isolated the meristematic and elongation zones of Col-0, upb1-1 mutant and 35S::UPB1-3YFP/upb1-1 plants by micro-dissection and extracted RNA from each section independently.
Transcriptional regulation of ROS controls transition from proliferation to differentiation in the root.
Age, Specimen part
View SamplesTCP transcription factors from the CYC2-class are involved in the development of monosymmetric flowers in all core eudicot species analysed so far. In Antirrhinum majus, the CYC2/TCP transcription factor CYCLOIDEA (CYC) is the molecular key regulator driving the development of flower monosymmetry (Luo D, Carpenter R, Vincent C, Copsey L, Coen E: Origin of floral asymmetry in Antirrhinum. Nature 1996, 383:794-799). In the Brassicaceae Iberis amara, a stronger expression of the CYC2 gene IaTCP1 in the small adaxial petals likely leads to the reduced petal size in comparison to large abaxial petals, with hardly any IaTCP1 expression. This results in the formation of the monosymmetric Iberis flower (Busch A, Zachgo S: Control of corolla monosymmetry in the Brassicaceae Iberis amara. PNAS 2007, 104:16714-16719). In contrast, the orthologous TCP/CYC2 transcription factor TCP1 from Arabidopsis thaliana, which forms equally sized and shaped petal pairs, only shows an early and transient expression in the adaxial area of floral primordia. This implies that monosymmetry in the Brassicaceae evolved through a heterochronic expression shift of the TCP/CYC2 key regulator gene IaTCP1.
Differential transcriptome analysis reveals insight into monosymmetric corolla development of the crucifer Iberis amara.
Specimen part
View SamplesStandard chemotherapy is the only systemic treatment for triple-negative breast cancer (TNBC). Despite the good initial responses, resistance remains a major therapeutic obstacle. Here, we employed a High-Throughput Screen to identify targeted therapies that overcome chemoresistance in TNBC. We applied short-term paclitaxel treatment and screened 320 small-molecule inhibitors of known targets to identify drugs that preferentially and efficiently target paclitaxel-treated TNBC cells. Among these compounds the SMAC mimetics (BV6, Birinapant) and BH3-mimetics (ABT-737/263) were recognized as potent targeted therapy for multiple paclitaxel-residual TNBC cell lines. However, acquired paclitaxel resistance through repeated paclitaxel pulses result in desensitization to BV6, but not to ABT-263, suggesting that short- and long-term paclitaxel resistance are mediated by distinct mechanisms. Gene expression profiling of paclitaxel-residual, -resistant and nave MDA-MB-231 cells demonstrated that paclitaxel-residual, as opposed to -resistant cells, were characterized by an apoptotic signature, with downregulation of anti-apoptotic genes (BCL2, BIRC5), activation of apoptosis inducers (IL24, PDCD4), and enrichment of TNF/NF-B pathway, including upregulation of TNFSF15, coupled with cell-cycle arrest. BIRC5 and FOXM1 downregulation and IL24 induction was also evident in breast cancer patient datasets following taxane treatment. Exposure of nave and paclitaxel-resistant cells to supernatants of paclitaxel-residual cells sensitized them to BV6, and treatment with TNF enhanced the potency of BV6, suggesting that sensitization to BV6 is mediated, at least partially, by secreted factor(s). Our results suggest that administration of SMAC or BH3 mimetics following short-term paclitaxel treatment could be an effective therapeutic strategy for TNBC, while only BH3-mimetics could effectively overcome long-term paclitaxel resistance
Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxel-resistant triple negative breast cancer cells.
Sex, Age, Specimen part, Cell line, Treatment
View SamplesSmac mimetics are considered as promising cancer therapeutics, but little is yet known about how they alter gene expression. In this study we used an unbiased genome-wide expression array to investigate Smac mimetic BV6-induced gene regulation in breast cancer cell lines. Kinetic analysis revealed that BV6 alters gene expression in two waves. The first wave primarily involves NF-B- and AP-1 families of transcription factors, while the second wave largely depends on tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, disrupting auto-/paracrine tumor necrosis factor- (TNF)/ (TNFR1) signaling by knockdown of TNFR1 strongly attenuates the BV6-induced second wave of gene expression and upregulation of many pathways including NF-B signaling, apoptosis and immune signalling, but not MAPK signaling pathways. Consistently, BV6 stimulates phosphorylation of cJun, a marker of MAPK cascade activation, irrespective of the presence or absence of the TNF blocking antibody Enbrel. We show here in a comprehensive overview that BV6-induced gene expression in breast cancer cells takes place in a time- as well as TNFR1-dependent manner.
Smac mimetic induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFR1 signaling.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
View SamplesTranscriptional profile of whole roots of wild-type and pye-1 mutants exposed to 24 hours -Fe were generated
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
View SamplesNitric oxide (NO) regulated pulmonary vascular function and structure, in part, via its effect on gene expression. We used microarrays to determine the up- and downregulated genes in rat pulmonary artery smooth muscle cells exposed to the NO donor S-nitrosoglutathione (GSNO) for 1, 2, and 4 hours.
Phosphodiesterase 3A expression is modulated by nitric oxide in rat pulmonary artery smooth muscle cells.
Specimen part
View Samples