MicroRNA profiling of lung adenocarcinomas, induced by cRaf overexpression in lung epithelium (Affymetrix)
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Valerio Del Vescovo
PROVIDER: E-GEOD-50748 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In this study we analyzed the expression of miRNAs in the lungs of SP-C/c-raf transgenic mice. The transgene is under the transcriptional control of the surfactant protein C (SP-C) promoter and consists of the oncogenically activated NH2-terminal deletion mutant c-Raf-1-BxB. Overall this study aims at identifying miRNAs regulated in precursor lesions of lung cancer. Agilent platform was used to analyze and compare the miRNA expression pattern in RNA extracts derived from two different conditions, i.e. lung of wild type mice and lung of SP-C/c-raf mice expressing the c-Raf-1 transgene. Each gender and condition was tested separately using 6 different individuals from each group: male and female wild type mice (M WT and F WT) and male and female transgenic mice (M c-Raf and F c-Raf).
2013-09-11 | E-GEOD-50752 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-09-11 | E-GEOD-50753 | biostudies-arrayexpress
Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-ß superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-ß has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-ß action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing IVD and to begin to understand the mechanism of TGF-ß action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice. Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/ database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We propose TGF-ß has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-ß that warrant further investigation as regulators of IVD development. Thirteen samples were analyzed. This includes three biological replicates of laser captured IVD from E13.5 day control mice, three biological replicates of laser captured vertebrae from the same E13.5 day control mice, three biological relicates of laser captured vertebrae from E13.5 day Col2aCre;Tgfbr2lox/lox mice, and four biological replicates of laser captured IVD from E13.5 day Col2aCre;Tgfbr2lox/lox mice.
2010-04-09 | E-GEOD-18647 | biostudies-arrayexpress
Project description:Chronic stress is a key risk factor for a variety of diseases, but the determinants of individual stress susceptibility are still unclear. Using a recently developed paradigm for chronic social stress in mice we identified animals that were resistant or susceptible to the persistent effects of chronic stress exposure. Gene expression analysis in laser-microdissected hippocampal subfields of both groups revealed differentially regulated AMPA receptor subunits, which might affect the susceptibility of an individual to chronic social stress. To test this hypothesis, animals were treated with the AMPA receptor potentiator LY451646 or vehicle during the last 4 weeks of chronic stress exposure. Enhanced AMPA receptor function in chronically stressed animals ameliorated the lasting effects of the chronic stress exposure on physiological, neuroendocrine and behavioural parameters. Our data suggest that differences in AMPA receptor function may underlie individual stress susceptibility and support AMPA receptor potentiators as potential medication in stress-related diseases. Keywords: phenotype, chronic stress, AMPA We have subjected 120 individuals to the chronic social stress procedure, which was recently shown to result in robust effects on neuroendocrine and behavioural parameters (Sterlemann V, 2008). Following the stress procedure all animals were single housed for 7 days. Corticosterone secretion was significantly increased in the chronic stress group compared to controls after one week of single housing. Within the chronic stress group we observed a large variation, where some individuals had recovered from the stress procedure, while others still showed a largely increased corticosterone secretion. After 4 more weeks of single housing, the difference in basal corticosterone secretion between the animals susceptible to chronic stress and unsusceptible or control subjects was still evident. From the group extremes in the chronically stressed animals we selected the 6 most-affected and the 6 most resistant individuals. To investigate the mechanisms underlying the observed differences in individual stress susceptibility between these mice we laser dissected the CA1 and the dentate gyrus region of the hippocampus in the selected mice and performed a gene expression profiling analysis. Pooled amplified RNA samples were then hybridised on Illumina mouse BeadChips (N=4 per group) and detected in the Illumina BeadArray Reader (Illumina, Inc., San Diego, CA).
2010-10-25 | E-GEOD-11211 | biostudies-arrayexpress
Project description:Gene expression profiling of normal tissues after curative radiotherapy was carried out to investigate the pathogenesis of late radiation injury in humans. Irradiated and control normal breast tissue was collected from patients undergoing bilateral mastectomy for ipsilateral tumour relapse or prophylaxis following radiotherapy for breast cancer. Using P.A.L.M. laser capture microdissection (LCM) of frozen sections, breast tissue was separated into an epithelial compartment (terminal duct lobular units and ducts) and a stromal compartment (remaining tissue). RNA was extracted, amplified and hybridised to a 20k cDNA array against a breast tissue reference RNA. Expression profiles of irradiated vs control breast were compared for each tissue compartment
2008-08-12 | E-TABM-419 | biostudies-arrayexpress
Project description:Esophageal adenocarcinoma (EAC) has the fastest increase of any cancer in the US and Europe, and arises in the setting of BarrettM-bM-^@M-^Ys esophagus (BE), defined by replacement of normal squamous epithelium with columnar intestinal-like epithelium. BE is thought to result from chronic esophageal inflammation but has been elusive to model in animals. Herein, we have generated the first transgenic mouse model of BarrettM-bM-^@M-^Ys esophagus through overexpression of interleukin-1M-CM-^_ (IL-1M-NM-2). IL-1M-NM-2 overexpression in the mouse esophageal mucosa induces chronic inflammation that progresses to intestinal metaplasia, with characteristic expression of TFF2, Bmp4 and Cdx2. With aging, IL-1b transgenic mice progress to esophageal adenocarcinoma (EAC) but the process is markedly accelerated by exposure to bile acids and/or nitrosamines, resembling the human counterpart. Moreover, progenitor cells present in the gastric cardia, but absent from the esophagus in humans and mice, are increased in BE, suggesting the cell of origin in the gastric cardia Comparison of BE and EAC tissue from the mouse with normal squamous epithelium from the mouse.
2011-01-31 | E-GEOD-24931 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE18647: Gene expression in embryonic intervertebral disc and vertebrae. GSE18648: TGF-beta and BMP mediated gene expression in cultured sclerotome. Refer to individual Series
2010-04-09 | E-GEOD-18649 | biostudies-arrayexpress
Project description:Tertiary lymphoid organs (TLOs) emerge in response to nonresolving inflammation but their roles in adaptive immunity remain unknown. Here, we explored artery TLOs (ATLOs) to delineate atherosclerosis T cell responses in apoe-/- mice during aging. Though the T cell repertoire showed systemic age-associated contractions in size and modifications in subtype composition and activation, wt and apoe-/- mice were equally affected. In contrast, ATLOs - but not wt aortae, apoe-/- aorta segments without ATLOs or atherosclerotic plaques - promoted T cell recruitment, altered characteristics of T cell motility, primed and imprinted T cells in situ, generated CD4+/FoxP3-, CD4+/FoxP3+, CD8+/FoxP3- effector and central memory cells, and converted naïve CD4+/FoxP3- T cells into induced Treg cells. ATLOs also showed substantially increased antigen presentation capability by conventional dendritic cells (DCs) and monocyte-derived DCs but not by plasmacytoid DCs. Thus, the senescent immune system specifically employs ATLOs to control dichotomic atherosclerosis T cell immune responses. We assembled transcriptome maps of wt and apoe-/- aortae and aorta-draining RLNs and identified ATLOs as major sites of atherosclerosis-specific T cell responses during aging: Transcriptome atlases of wt and apoe-/- abdominal aortae and associated draining RLNs were constructed from laser capture microdissection (LCM)-based whole genome mRNA expression microarrays yielding 6 maps: wt adventitia (tissue-1); wt RLN (tissue-2); apoe-/- ATLOs (tissue-3); apoe-/- RLN (tissue-4); apoe-/- adventitia without adjacent plaques (tissue-5), and plaques (tissue-6). Several two-tissue comparisons within the transcriptome atlases are noteworthy: Unexpectedly, transcriptomes of wt and apoe-/- RLNs were virtually identical; additonal data revealed that transcriptomes of RLNs were strikingly similar to those of inguinal LNs which do not drain the aorta adventitia (as shown of India ink injection experiments of surgically exposed aortae); in sharp contrast, wt adventitia versus ATLOs revealed 1405 differentially expressed transcripts many of which encoded members of GO terms immune response and inflammatory response; the ATLO-plaque comparison also showed > 1000 differentially expressed transcripts; however, wt adventitia versus apoe-/- adventitia without plaque showed few genes (< 5 % of differentially expressed transcripts of the wt adventitia-ATLO comparison). Thus, the aorta transcriptome atlases support the conclusion that neither aorta-draining apoe-/- RLNs nor ILNs participate in atherosclerosis-specific T cell responses. In addition, they demonstrate that T cell responses in the diseased aorta are highly territorialized. Finally, these data show that the immune responses carried out in ATLOs differ significantly from those carried out in plaques. We next identified three major clusters within the transcriptome atlases through ANOVA analyses and application of strict filters: An adventitia cluster, a plaque/ATLO cluster, and a LN/plaque cluster. The total number of differentially expressed genes in each cluster were examined for GO terms immune response, inflammatory response, T cell activation, positive regulation of T cell response, and T cell proliferation. Within the adventitia cluster, similarities of transcriptomes of wt adventitia and apoe-/- adventitia without associated plaque versus ATLOs indicate that a robust number of immune response-regulating genes are selectively expressed in ATLOs which are located within a distance of few µm of the adventitia without associated plaques indicating a very high degree of territoriality of the atherosclerosis T cell response. Furthermore, unlike the total number of differentially regulated transcripts, the majority of transcripts among GO terms immune response and inflammatory response, was up-regulated. Inspection of the plaque/ATLO cluster provided further information: The majority of immune response regulating genes where expressed at a higher level in ATLOs when compared to plaques though plaques also contained a significant number of immune response regulating genes; the reverse is true for genes regulating inflammation. Finally, the lymph node cluster revealed that though the majority of immune response regulating genes resides in both wt and apoe-/- RLNs (with little differences between them) ATLOs express a selected set of immune response regulating genes at a higher level when compared to LNs. In addition, the inflammatory component of ATLOs when compared to LNs is documented by the finding that many more genes regulating inflammation reside in ATLOs even when compared to those of plaques. Key words: T cell response in atherosclerosis; Laser capture microdissection; transcriptome atlas of atherosclerosis. Citations: Gräbner R. et al. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J Exp Med 2009 Jan 16;206(1):233-48. PMID: 19139167; Moos M. et al. The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2386-91. Epub 2005 Sep 22. PMID: 16179593; Beer M. et al. Laser-capture microdissection of hyperlipidemic/ApoE-/- mouse aorta atherosclerosis. Methods Mol Biol. 2011;755:417-28. PMID: 21761324; Weih F. et al. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis. Front Physiol. 2012;3:226. Epub 2012 Jul 6. PMID: 22783198. Wild-type and apoE-deficient mice on the C57BL/6J genetic background were maintained on a standard mouse chow. Total aortae were removed at the age of 6 (n=3), 32 (n=3), or 78 (n=3) w and microarrays were prepared from total RNA extracts or extracts of atherosclerotic lesions and adventitiae obtained by the use of a laser dissection microscope. In addition, aorta associated LNs or distant LNs were prepared from both mouse genotypes.
2013-10-30 | E-GEOD-40156 | biostudies-arrayexpress
Project description:Atherosclerosis is a transmural chronic inflammatory condition of small and large arteries that is associated with adaptive immune responses at all disease stages. However, impacts of adaptive immune reactions on clinically apparent atherosclerosis such as intima lesion (plaque) rupture, thrombosis, myocardial infarction, and aneurysm largely remain to be identified. It is increasingly recognized that leukocyte infiltrates in plaque, media, and adventitia are distinct but their specific roles have not been defined. To map these infiltrates, we employed laser capture microdissection (LCM) to isolate the three arterial wall laminae using apoE-/- mouse aorta as a model. RNA from LCM-separated tissues was extracted and large scale whole genome expression microarrays were prepared. We observed that the quality of the resulting gene expression maps was compromised by tissue RNA carried over from adjacent laminae during LCM. To account for these flaws, we established quality controls and algorithms to improve the predictive power of LCM-derived microarray data. Our approach creates robust transcriptome atlases of normal and atherosclerotic aorta. Assessing LCM transcriptomes for immunity-related mRNAs indicated markedly distinctive gene expression patterns in the three laminae of the atherosclerotic aorta. These mouse mRNA expression data banks can now be mined to address a wide range of questions in cardiovascular biology. Wild-type and apoE-deficient mice on the C57BL/6J genetic background were maintained on a standard mouse chow. Total aortae were removed at the age of 78 weeks, abdominal aorta was separated from the remainder of the tissue and arterial wall laminae were separated by laser capture microdissection as described (Beer et al. 2011). Following RNA quality controls, microarrays were prepared following MIAME guidelines as described previously (Uzonyi et al. 2006; Graebner et al. 2009; Lotzer et al. 2010).
2011-11-03 | E-GEOD-21419 | biostudies-arrayexpress
Project description:To understand the role of miR-34a in oncogene-induced senescence, we tested global mRNA expression using microarrays of TIG3 TERT/ deltaB-RAF:ER cells transfected with a miR-34a LNA inhibitor or a scrambled control LNA in the presence or absence of deltaB-RAF activation.<br>TIG3 TERT/ deltaB-RAF:ER cells are primary human diploid fibroblasts immortalized by hTERT. deltaB-RAF is constitutively active due to truncation of the regulatory N-terminal domain and fused to the hormone-binding domain of the oestrogen receptor, which was modified to respond to 4-hydroxytamoxifen (4-OHT) but not beta-estradiol.<br>TIG3 TERT/ deltaB-RAF:ER cells were treated with 500nM 4-OHT or equal amounts of ethanol the day after seeding at 1E6 per 10cm plate, in three biological replicates. After 2 days of 4-OHT treatment, cells were transfected with LNA-miR-34a or a control LNA-scramble using Lipofectamine 2000 (Invitrogen). Total RNA was harvested 24 h post-transfection (3 days of 4-OHT treatment in total) using TRIzol reagent. Affymetrix microarray analysis (HG-U133 Plus 2.0 human) was performed.
2009-08-01 | E-MEXP-2241 | biostudies-arrayexpress