Transcription profiling of human breast stroma and epithelium after curative radiotherapy to investigate the pathogenesis of late radiation injury in humans
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Scanning hardware
ORGANISM(S): Homo sapiens
SUBMITTER: Anita Grigoriadis
PROVIDER: E-TABM-419 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2022-05-20 | PXD029979 | Pride
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:Pancreatic Ductal Adenocarcinoma (PDA) is a critical health issue in cancer field with little new therapeutic options. Several evidences support an implication of intra-tumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within pathophysiology and clinical course of PDA, mainly through tumor recurrence and neuropathic pain, remains unknown neglecting a putative therapeutic window. Here, we report that intra-tumoral microenvironment is a mediator of PDA Associated Neural Remodeling (PANR). With laser capture microdissection of stromal/tumoral compartment from human PDA followed by cDNA based microarray analyses we highlighted numerous factors expressed by stromal compartment that could impact on neuroplastic changes; among them, the Slit2/Robo axon guidance pathway. Using co-culture in vitro, we showed that stromal secreted Slit2 increases DRG neurite outgrowth and Schwann cells migration/proliferation by modulating N-Cadherin/β-Catenin signaling. Importantly, Slit2/Robo signaling inhibition disrupts this stromal/neural connection. Finally, we revealed in vivo that Slit2 expression is correlated with neural remodeling within Human and mouse PDA. These results demonstrate the implication of microenvironment, through secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of stromal/neural compartment dialogue by using Slit2/Robo pathway inhibitors for treatment of pancreatic cancer recurrence and associated pain. Freshly frozen tissue samples of PDACs were obtained from patients who underwent surgery. Patients underwent hemipancreaticoduodenectomy or distal pancreatectomy. No distant metastases were revealed at initial diagnosis. Histological examination confirmed diagnosis of PDAC in all cases. Prior to surgery all patients had signed an informed consent form that had been approved by the local ethics committee. Frozen sections were obtained from tissue samples of three tumors. After a brief staining sections were dehydrated and epithelial and stromal compartment has been microdissected using the PALM system. The microdissected material was immediately dissolute in a buffer containing β-mercaptoethanol and RNA carrier, and frozen before RNA extraction. Fifteen ug of total RNA was converted to biotinylated cRNA and hybridised to a human oligonucleotide array U133 Plus 2.0 (Genechip, Affymetrix, Santa Clara, CA).
2015-07-01 | E-GEOD-50570 | biostudies-arrayexpress
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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: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. Affymetrix 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-50748 | 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
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2011-11-03 | E-GEOD-21419 | 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
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