المؤلفون: Sandra Andersson, Kenneth Nilsson, Linn Fagerberg, Björn M Hallström, Christer Sundström, Angelika Danielsson, Karolina Edlund, Mathias Uhlen, Anna Asplund

المصدر: PLoS ONE, Vol 9, Iss 12, p e115911 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: BackgroundThe sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics.ResultsAn enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59.ConclusionsIn this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/fbdcd78b2714437e8c1631f4bd3c7fe2Test

المؤلفون: Angelika Danielsson, Fredrik Pontén, Linn Fagerberg, Björn M Hallström, Jochen M Schwenk, Mathias Uhlén, Olle Korsgren, Cecilia Lindskog

المصدر: PLoS ONE, Vol 9, Iss 12, p e115421 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4278897?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/f81301248e1749aab59ccf53dd85ea1cTest

المؤلفون: Angelika Danielsson, Helena Dzojic, Victoria Rashkova, Wing-Shing Cheng, Magnus Essand

المصدر: PLoS ONE, Vol 6, Iss 2, p e14700 (2011)

مصطلحات موضوعية: Medicine, Science

الوصف: The histone deacetylase inhibitor FK228 has previously been shown to enhance adenoviral transgene expression when cells are pre-incubated with the drug. Upregulation of the coxsackie adenovirus receptor (CAR), leading to increased viral transduction, has been proposed as the main mechanism. In the present study, we found that the highest increase in transgene expression was achieved when non-toxic concentrations of FK228 were added immediately after transduction, demonstrating that the main effect by which FK228 enhances transgene expression is transduction-independent. FK228 had positive effects both on Ad5 and Ad5/f35 vectors with a variety of transgenes and promoters, indicating that FK228 works mainly by increasing transgene expression at the transcriptional level. In some cases, the effects were dramatic, as demonstrated by an increase in CD40L expression by FK228 from 0.3% to 62% when the murine prostate cancer cell line TRAMP-C2 was transduced with Ad[CD40L]. One unexpected finding was that FK228 decreased the transgene expression of an adenoviral vector with the prostate cell-specific PPT promoter in the human prostate adenocarcinoma cell lines LNCaP and PC-346C. This is probably a consequence of alteration of the adenocarcinoma cell lines towards a neuroendocrine differentiation after FK228 treatment. The observations in this study indicate that FK228 enhances adenoviral therapy by a transduction-independent mechanism. Furthermore, since histone deacetylase inhibitors may affect the differentiation of cells, it is important to keep in mind that the activity and specificity of tissue- and tumor-specific promoters may also be affected.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3040751?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/ff59be40d7c8422cbece563a9e614932Test

المؤلفون: Uptec X Issn, Angelika Danielsson, Molecular Biotechnology Programme, Magnus Essand, Catharina Svensson

المساهمون: The Pennsylvania State University CiteSeerX Archives

المصدر: http://www.ibg.uu.se/digitalAssets/91/91714_DanielssonTest-Angelika-arbete.pdf.

مصطلحات موضوعية: gene therapy, adenovirus, insulator, AdEasy ™ vector system, luciferase assay

الوصف: Prostate cancer gene therapy based on an adenoviral vector with tissue specific expression

وصف الملف: application/pdf

العلاقة: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.461.9997Test; http://www.ibg.uu.se/digitalAssets/91/91714_DanielssonTest-Angelika-arbete.pdf

الإتاحة: http://www.ibg.uu.se/digitalAssets/91/91714_DanielssonTest-Angelika-arbete.pdf

المؤلفون: Olof Eriksson, Olle Korsgren, Lars Johansson, Paul Czernichow, Ewa Hellström-Lindahl, Angelika Danielsson, Fredrik Pontén

المصدر: Acta Diabetologica. 53:413-421

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Receptors, Prostaglandin, Cell, Biology, Flow cytometry, 03 medical and health sciences, Endocrinology, Cell Line, Tumor, Insulin-Secreting Cells, Internal medicine, Diabetes Mellitus, Internal Medicine, medicine, Animals, Humans, Receptors, Immunologic, Beta (finance), Receptor, medicine.diagnostic_test, HEK 293 cells, General Medicine, Ligand (biochemistry), Rats, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, Organ Specificity, Vesicular Monoamine Transport Proteins, Cancer research, Beta cell, Pancreas, Biomarkers

الوصف: To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2.GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ.GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ.GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7e4e080504dbf8e88daaaa3f3c358701Test
https://doi.org/10.1007/s00592-015-0811-3Test

المؤلفون: Stella Korsgren, Anna Wiberg, Oskar Skog, Bjørn Edwin, Trond Buanes, Olle Korsgren, Angelika Danielsson, Lars Krogvold, Knut Dahl-Jørgensen

المصدر: The American Journal of Pathology. 185:129-138

مصطلحات موضوعية: Adult, medicine.medical_specialty, Adolescent, Genes, MHC Class I, Human leukocyte antigen, Biology, Enhanceosome, Pathology and Forensic Medicine, Islets of Langerhans, Young Adult, NLRC5, Internal medicine, medicine, Humans, Endocrine system, Child, Aged, Type 1 diabetes, geography, geography.geographical_feature_category, Intracellular Signaling Peptides and Proteins, Middle Aged, medicine.disease, Islet, Pancreas, Exocrine, Diabetes Mellitus, Type 1, Real-time polymerase chain reaction, Endocrinology, Immunology, Immunohistochemistry, Interferons, Transcriptome, Transcription Factors

الوصف: The cause of type 1 diabetes remains unknown. To dissect the link between hyperexpression of human leukocyte antigen (HLA) class I on the islet cells, we examined its expression in subjects with recent-onset type 1 diabetes. IHC showed seemingly pronounced hyperexpression in subjects with recent-onset type 1 diabetes, as well as in some nondiabetic subjects. In all subjects, HLA class I expression on exocrine tissue was low. However, no difference in the level of HLA class I expression was found between islet and exocrine tissue using Western blot, flow cytometry, real-time quantitative PCR, or RNA sequencing analyses. Also, the level of HLA class I expression on the messenger level was not increased in islets from subjects with recent-onset type 1 diabetes compared with that in nondiabetic subjects. Consistently, the HLA class I specific enhanceosome (NLRC5) and related transcription factors, as well as interferons, were not enhanced in islets from recent-onset type 1 diabetic subjects. In conclusion, a discrepancy in HLA class I expression in islets assessed by IHC was observed compared with that using quantitative techniques showing similar expression of HLA class I in islets and exocrine tissue in subjects with recent-onset type 1 diabetes, nor could any differences be found between type 1 diabetic and nondiabetic subjects. Results presented provide important clues for a better understanding on how this complex disease develops.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74762af06fb0f45cf8b84efbcdfd3c9aTest
https://doi.org/10.1016/j.ajpath.2014.09.004Test

المؤلفون: Mathias Uhlén, Per-Henrik Edqvist, Karolina Edlund, Björn M. Hallström, Fredrik Pontén, Linn Fagerberg, Angelika Danielsson

المصدر: Journal of Histochemistry & Cytochemistry. 63:129-141

مصطلحات موضوعية: Proteomics, Cell type, Histology, Protein Array Analysis, Human Protein Atlas, Human skin, Biology, Antibodies, Transcriptome, Esophagus, Gene expression, Humans, Skin, integumentary system, Sequence Analysis, RNA, Gene Expression Profiling, Articles, Fibroblasts, Molecular biology, Cell biology, Gene expression profiling, Epidermal Cells, Organ Specificity, Langerhans Cells, Proteome, Melanocytes, Epidermis, Anatomy

الوصف: To increase our understanding of skin, it is important to define the molecular constituents of the cell types and epidermal layers that signify normal skin. We have combined a genome-wide transcriptomics analysis, using deep sequencing of mRNA from skin biopsies, with immunohistochemistry-based protein profiling to characterize the landscape of gene and protein expression in normal human skin. The transcriptomics and protein expression data of skin were compared to 26 (RNA) and 44 (protein) other normal tissue types. All 20,050 putative protein-coding genes were classified into categories based on patterns of expression. We found that 417 genes showed elevated expression in skin, with 106 genes expressed at least five-fold higher than that in other tissues. The 106 genes categorized as skin enriched encoded for well-known proteins involved in epidermal differentiation and proteins with unknown functions and expression patterns in skin, including the C1orf68 protein, which showed the highest relative enrichment in skin. In conclusion, we have applied a genome-wide analysis to identify the human skin-specific proteome and map the precise localization of the corresponding proteins in different compartments of the skin, to facilitate further functional studies to explore the molecular repertoire of normal skin and to identify biomarkers related to various skin diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d332231d854010adaf91ed4cc9dba08Test
https://doi.org/10.1369/0022155414562646Test

المؤلفون: Björn M. Hallström, Fredrik Pontén, Angelika Danielsson, Mathias Uhlén, Linn Fagerberg, Dijana Djureinovic, Cecilia Lindskog

المصدر: MHR: Basic science of reproductive medicine. 20:476-488

مصطلحات موضوعية: Adult, Male, Embryology, Proteome, Biology, Antibodies, Transcriptome, Spermatocytes, Genetics, Humans, Spermatogenesis, Molecular Biology, Sertoli Cells, Gene Expression Profiling, Leydig Cells, Obstetrics and Gynecology, RNA, Cell Biology, Middle Aged, Immunohistochemistry, Spermatids, Molecular biology, Spermatogonia, Cell biology, Reproductive Medicine, Organ Specificity, biology.protein, Ploidy, Antibody, Developmental biology, Developmental Biology

الوصف: The testis' function is to produce haploid germ cells necessary for reproduction. Here we have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to characterize the molecular components of the testis. Deep sequencing (RNA-Seq) of normal human testicular tissue from seven individuals was performed and compared with 26 other normal human tissue types. All 20 050 putative human genes were classified into categories based on expression patterns. The analysis shows that testis is the tissue with the most tissue-specific genes by far. More than 1000 genes show a testis-enriched expression pattern in testis when compared with all other analyzed tissues. Highly testis enriched genes were further characterized with respect to protein localization within the testis, such as spermatogonia, spermatocytes, spermatids, sperm, Sertoli cells and Leydig cells. Here we present an immunohistochemistry-based analysis, showing the localization of corresponding proteins in different cell types and various stages of spermatogenesis, for 62 genes expressed at50-fold higher levels in testis when compared with other tissues. A large fraction of these genes were unexpectedly expressed in early stages of spermatogenesis. In conclusion, we have applied a genome-wide analysis to identify the human testis-specific proteome using transcriptomics and antibody-based protein profiling, providing lists of genes expressed in a tissue-enriched manner in the testis. The majority of these genes and proteins were previously poorly characterised in terms of localization and function, and our list provides an important starting point to increase our molecular understanding of human reproductive biology and disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9a96b86903cd1a5ba114b3f38543d13Test
https://doi.org/10.1093/molehr/gau018Test

المؤلفون: Olle Korsgren, Lars Johansson, Cecilia Lindskog, Jan W. Eriksson, Angelika Danielsson, Fredrik Pontén

المصدر: Journal of Proteomics. 75:2611-2620

مصطلحات موضوعية: Proteomics, Receptors, Prostaglandin, Biophysics, Human Protein Atlas, Biochemistry, Antibodies, Antigen, Insulin-Secreting Cells, medicine, Guanine Nucleotide Exchange Factors, Humans, Insulin, Receptors, Immunologic, Databases, Protein, Serpins, Membrane Glycoproteins, Microscopy, Confocal, biology, Colocalization, Glucagon, Immunohistochemistry, Molecular biology, Transmembrane protein, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Platelet Glycoprotein GPIb-IX Complex, Immunology, biology.protein, Beta cell, Antibody, Pancreas, Biomarkers

الوصف: Beta cell-specific surface targets are required for non-invasive monitoring of beta cell mass, which could be used for evaluation of new diabetes treatments as well as to help unravel pathogenic mechanisms underlying beta cell dysfunction. By antibody-based proteomics, we have identified and explored a set of islet cell-specific proteins. A search algorithm in the Human Protein Atlas was set up for identification of islet-specific proteins that yielded 27 hits, of which twelve showed a clear membranous expression pattern or had predicted transmembrane regions. The specificity of the identified proteins was investigated by immunohistochemical staining of pancreas sections from diabetic and non-diabetic subjects. No expression of these antigens could be detected in the exocrine pancreas. Colocalization with insulin and glucagon was further determined by confocal microscopy using isolated human islets. All antibodies specifically stained human islets and colocalization analysis revealed that four proteins were exclusively expressed in beta cells. Importantly, these antibodies were negative in sections from subjects with long-standing type 1 diabetes. In the present study, we present four proteins; DGCR2, GBF1, GPR44 and SerpinB10, the expression of which has not previously been described in beta cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6978309a4af89c5e877ce95a8800e8e6Test
https://doi.org/10.1016/j.jprot.2012.03.008Test

المؤلفون: Karen F. Chambers, Lindsay J. Georgopoulos, Corrina M.A. de Ridder, Magnus Essand, Angelika Danielsson, Chris H. Bangma, Regina M. Leadley, Helen Evans, Wytske M. van Weerden, Martha Simpson-Holley, Robert Kraaij, Norman J. Maitland

المساهمون: Urology, Internal Medicine

المصدر: Human Gene Therapy, 21(7), 815-827. Mary Ann Liebert Inc.

مصطلحات موضوعية: Male, Genetic enhancement, Genetic Vectors, Bioinformatics, Models, Biological, Prostate cancer, SDG 3 - Good Health and Well-being, In vivo, Cell Line, Tumor, Genetics, Animals, Humans, Medicine, Vector (molecular biology), Molecular Biology, Neoplasm Staging, Clinical Trials as Topic, business.industry, Genetic transfer, Prostatic Neoplasms, Cancer, Genetic Therapy, medicine.disease, Clinical trial, Cancer cell, Immunology, Molecular Medicine, business

الوصف: Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4f252c055bfb9094d4a455834ef62aaTest
https://doi.org/10.1089/hum.2009.210Test