@article {701, title = {CSVS, a crowdsourcing database of the Spanish population genetic variability.}, journal = {Nucleic Acids Res}, volume = {49}, year = {2021}, month = {2021 01 08}, pages = {D1130-D1137}, abstract = {

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network. CSVS can be accessed at: http://csvs.babelomics.org/.

}, keywords = {Alleles, Chromosome Mapping, Crowdsourcing, Databases, Genetic, Exome, Gene Frequency, Genetic Variation, Genetics, Population, Genome, Human, Genomics, Humans, Internet, Precision Medicine, Software, Spain}, issn = {1362-4962}, doi = {10.1093/nar/gkaa794}, author = {Pe{\~n}a-Chilet, Maria and Rold{\'a}n, Gema and Perez-Florido, Javier and Ortuno, Francisco M and Carmona, Rosario and Aquino, Virginia and L{\'o}pez-L{\'o}pez, Daniel and Loucera, Carlos and Fernandez-Rueda, Jose L and Gallego, Asunci{\'o}n and Garcia-Garcia, Francisco and Gonz{\'a}lez-Neira, Anna and Pita, Guillermo and N{\'u}{\~n}ez-Torres, Roc{\'\i}o and Santoyo-L{\'o}pez, Javier and Ayuso, Carmen and Minguez, Pablo and Avila-Fernandez, Almudena and Corton, Marta and Moreno-Pelayo, Miguel {\'A}ngel and Morin, Mat{\'\i}as and Gallego-Martinez, Alvaro and Lopez-Escamez, Jose A and Borrego, Salud and Anti{\v n}olo, Guillermo and Amigo, Jorge and Salgado-Garrido, Josefa and Pasalodos-Sanchez, Sara and Morte, Beatriz and Carracedo, {\'A}ngel and Alonso, {\'A}ngel and Dopazo, Joaquin} } @article {710, title = {Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response.}, journal = {Genes (Basel)}, volume = {12}, year = {2020}, month = {2020 12 31}, abstract = {

Defective healing leading to cutaneous ulcer formation is one of the most feared complications of diabetes due to its consequences on patients{\textquoteright} quality of life and on the healthcare system. A more in-depth analysis of the underlying molecular pathophysiology is required to develop effective healing-promoting therapies for those patients. Major architectural and functional differences with human epidermis limit extrapolation of results coming from rodents and other small mammal-healing models. Therefore, the search for reliable humanized models has become mandatory. Previously, we developed a diabetes-induced delayed humanized wound healing model that faithfully recapitulated the major histological features of such skin repair-deficient condition. Herein, we present the results of a transcriptomic and functional enrichment analysis followed by a mechanistic analysis performed in such humanized wound healing model. The deregulation of genes implicated in functions such as angiogenesis, apoptosis, and inflammatory signaling processes were evidenced, confirming published data in diabetic patients that in fact might also underlie some of the histological features previously reported in the delayed skin-humanized healing model. Altogether, these molecular findings support the utility of such preclinical model as a valuable tool to gain insight into the molecular basis of the delayed diabetic healing with potential impact in the translational medicine field.

}, keywords = {Animals, Diabetes Mellitus, Experimental, Gene Expression Profiling, Gene Expression Regulation, Gene ontology, Humans, Metabolic Networks and Pathways, Mice, Mice, Nude, Microarray Analysis, Molecular Sequence Annotation, Principal Component Analysis, Signal Transduction, Skin, Skin Transplantation, Skin Ulcer, Streptozocin, Tissue Engineering, Transcriptome, Transplantation, Heterologous, Wound Healing}, issn = {2073-4425}, doi = {10.3390/genes12010047}, author = {Le{\'o}n, Carlos and Garcia-Garcia, Francisco and Llames, Sara and Garc{\'\i}a-P{\'e}rez, Eva and Carretero, Marta and Arriba, Mar{\'\i}a Del Carmen and Dopazo, Joaquin and Del Rio, Marcela and Escamez, Maria Jos{\'e} and Mart{\'\i}nez-Santamar{\'\i}a, Luc{\'\i}a} } @article {384, title = {Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis.}, journal = {Oncotarget}, volume = {8}, year = {2017}, month = {2017 Feb 14}, pages = {11589-11599}, abstract = {

The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cutaneous cells. We analysed the gene signature associated with RHC co-cultured melanocytes and keratinocytes by Protein-Protein interaction (PPI) network analysis to identify genes related with non-functional MC1R variants. From two detected networks, we selected 23 nodes as hub genes based on topological parameters. Differential expression of hub genes was then evaluated in healthy skin biopsies from RHC and black hair color (BHC) individuals. We also compared gene expression in melanoma tumors from individuals with RHC versus BHC. Gene expression in normal skin from RHC cutaneous cells showed dysregulation in 8 out of 23 hub genes (CLN3, ATG10, WIPI2, SNX2, GABARAPL2, YWHA, PCNA and GBAS). Hub genes did not differ between melanoma tumors in RHC versus BHC individuals. The study suggests that healthy skin cells from RHC individuals present a constitutive genomic deregulation associated with the red hair phenotype and identify novel genes involved in melanocyte biology.

}, keywords = {Adult, Coculture Techniques, Computational Biology, gene expression, Genetic Predisposition to Disease, Genomics, Hair Color, Humans, Keratinocytes, Melanocytes, Middle Aged, Phenotype, Receptor, Melanocortin, Type 1}, issn = {1949-2553}, doi = {10.18632/oncotarget.14140}, url = {http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget\&page=article\&op=view\&path\%5B\%5D=14140\&path\%5B\%5D=45094}, author = {Puig-Butille, Joan Anton and Gimenez-Xavier, Pol and Visconti, Alessia and Nsengimana, J{\'e}r{\'e}mie and Garcia-Garcia, Francisco and Tell-Marti, Gemma and Escamez, Maria Jos{\'e} and Newton-Bishop, Julia and Bataille, Veronique and Del Rio, Marcela and Dopazo, Joaquin and Falchi, Mario and Puig, Susana} } @article {433, title = {Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.}, journal = {Hum Mutat}, volume = {38}, year = {2017}, month = {2017 02}, pages = {148-151}, abstract = {

Congenital disorders of glycosylation (CDG) are a heterogeneous and rapidly growing group of diseases caused by abnormal glycosylation of proteins and/or lipids. Mutations in genes involved in the homeostasis of the endoplasmic reticulum (ER), the Golgi apparatus (GA), and the vesicular trafficking from the ER to the ER-Golgi intermediate compartment (ERGIC) have been found to be associated with CDG. Here, we report a patient with defects in both N- and O-glycosylation combined with a delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex. TRAPPIII is implicated in the anterograde transport from the ER to the ERGIC as well as in the vesicle export from the GA. This report expands the spectrum of genetic alterations associated with CDG, providing new insights for the diagnosis and the understanding of the physiopathological mechanisms underlying glycosylation disorders.

}, keywords = {Abnormalities, Multiple, Alleles, Amino Acid Substitution, Brain, Congenital Disorders of Glycosylation, Genotype, Humans, Magnetic Resonance Imaging, Male, mutation, Phenotype, Vesicular Transport Proteins, Whole Genome Sequencing}, issn = {1098-1004}, doi = {10.1002/humu.23145}, author = {Matalonga, Leslie and Bravo, Miren and Serra-Peinado, Carla and Garc{\'\i}a-Pelegr{\'\i}, Elisabeth and Ugarteburu, Olatz and Vidal, Silvia and Llambrich, Maria and Quintana, Ester and Fuster-Jorge, Pedro and Gonzalez-Bravo, Maria Nieves and Beltran, Sergi and Dopazo, Joaquin and Garcia-Garcia, Francisco and Foulquier, Fran{\c c}ois and Matthijs, Gert and Mills, Philippa and Ribes, Antonia and Egea, Gustavo and Briones, Paz and Tort, Frederic and Gir{\'o}s, Marisa} } @article {439, title = {Integrated gene set analysis for microRNA studies.}, journal = {Bioinformatics}, volume = {32}, year = {2016}, month = {2016 09 15}, pages = {2809-16}, abstract = {

MOTIVATION: Functional interpretation of miRNA expression data is currently done in a three step procedure: select differentially expressed miRNAs, find their target genes, and carry out gene set overrepresentation analysis Nevertheless, major limitations of this approach have already been described at the gene level, while some newer arise in the miRNA scenario.Here, we propose an enhanced methodology that builds on the well-established gene set analysis paradigm. Evidence for differential expression at the miRNA level is transferred to a gene differential inhibition score which is easily interpretable in terms of gene sets or pathways. Such transferred indexes account for the additive effect of several miRNAs targeting the same gene, and also incorporate cancellation effects between cases and controls. Together, these two desirable characteristics allow for more accurate modeling of regulatory processes.

RESULTS: We analyze high-throughput sequencing data from 20 different cancer types and provide exhaustive reports of gene and Gene Ontology-term deregulation by miRNA action.

AVAILABILITY AND IMPLEMENTATION: The proposed methodology was implemented in the Bioconductor library mdgsa http://bioconductor.org/packages/mdgsa For the purpose of reproducibility all of the scripts are available at https://github.com/dmontaner-papers/gsa4mirna

CONTACT: : david.montaner@gmail.com

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

}, keywords = {Computational Biology, Gene Expression Profiling, Gene ontology, Gene Regulatory Networks, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs, Neoplasms, Reproducibility of Results}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btw334}, author = {Garcia-Garcia, Francisco and Panadero, Joaquin and Dopazo, Joaquin and Montaner, David} } @article {450, title = {Screening of CD96 and ASXL1 in 11 patients with Opitz C or Bohring-Opitz syndromes.}, journal = {Am J Med Genet A}, volume = {170A}, year = {2016}, month = {2016 Jan}, pages = {24-31}, abstract = {

Opitz C trigonocephaly (or Opitz C syndrome, OTCS) and Bohring-Opitz syndrome (BOS or C-like syndrome) are two rare genetic disorders with phenotypic overlap. The genetic causes of these diseases are not understood. However, two genes have been associated with OTCS or BOS with dominantly inherited de novo mutations. Whereas CD96 has been related to OTCS (one case) and to BOS (one case), ASXL1 has been related to BOS only (several cases). In this study we analyze CD96 and ASXL1 in a group of 11 affected individuals, including 2 sibs, 10 of them were diagnosed with OTCS, and one had a BOS phenotype. Exome sequences were available on six patients with OTCS and three parent pairs. Thus, we could analyze the CD96 and ASXL1 sequences in these patients bioinformatically. Sanger sequencing of all exons of CD96 and ASXL1 was carried out in the remaining patients. Detailed scrutiny of the sequences and assessment of variants allowed us to exclude putative pathogenic and private mutations in all but one of the patients. In this patient (with BOS) we identified a de novo mutation in ASXL1 (c.2100dupT). By nature and location within the gene, this mutation resembles those previously described in other BOS patients and we conclude that it may be responsible for the condition. Our results indicate that in 10 of 11, the disease (OTCS or BOS) cannot be explained by small changes in CD96 or ASXL1. However, the cohort is too small to make generalizations about the genetic etiology of these diseases.

}, keywords = {Adolescent, Antigens, CD, Child, Child, Preschool, Craniosynostoses, Exome, Female, High-Throughput Nucleotide Sequencing, Humans, Infant, Intellectual Disability, Male, mutation, Pedigree, Phenotype, Prognosis, Repressor Proteins}, issn = {1552-4833}, doi = {10.1002/ajmg.a.37418}, author = {Urreizti, Roser and Roca-Ayats, Neus and Trepat, Judith and Garcia-Garcia, Francisco and Alem{\'a}n, Alejandro and Orteschi, Daniela and Marangi, Giuseppe and Neri, Giovanni and Opitz, John M and Dopazo, Joaquin and Cormand, Bru and Vilageliu, Llu{\"\i}sa and Balcells, Susana and Grinberg, Daniel} } @article {445, title = {Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer.}, journal = {Oncotarget}, volume = {7}, year = {2016}, month = {2016 Mar 15}, pages = {12904-16}, abstract = {

Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC).We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression.Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease.

}, keywords = {Adult, Aged, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Disease Progression, Female, Humans, Lung Neoplasms, Male, metabolomics, Middle Aged, Proton Magnetic Resonance Spectroscopy}, issn = {1949-2553}, doi = {10.18632/oncotarget.7354}, author = {Puchades-Carrasco, Leonor and Jantus-Lewintre, Eloisa and P{\'e}rez-Rambla, Clara and Garcia-Garcia, Francisco and Lucas, Rut and Calabuig, Silvia and Blasco, Ana and Dopazo, Joaquin and Camps, Carlos and Pineda-Lucena, Antonio} } @article {463, title = {Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations.}, journal = {Hum Mol Genet}, volume = {24}, year = {2015}, month = {2015 Jul 15}, pages = {4037-48}, abstract = {

Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype-phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and whole-exome sequencing led to the identification of a homozygous mutation (c.358_359delGT; p.Ala122Leufs*2) in the ZNF408 gene. A screening performed in 217 additional unrelated families revealed another homozygous mutation (c.1621C>T; p.Arg541Cys) in an isolated RP case. ZNF408 encodes a transcription factor that harbors 10 predicted C2H2-type fingers thought to be implicated in DNA binding. To elucidate the ZNF408 role in the retina and the pathogenesis of these mutations we have performed different functional studies. By immunohistochemical analysis in healthy human retina, we identified that ZNF408 is expressed in both cone and rod photoreceptors, in a specific type of amacrine and ganglion cells, and in retinal blood vessels. ZNF408 revealed a cytoplasmic localization and a nuclear distribution in areas corresponding with the euchromatin fraction. Immunolocalization studies showed a partial mislocalization of the p.Arg541Cys mutant protein retaining part of the WT protein in the cytoplasm. Our study demonstrates that ZNF408, previously associated with Familial Exudative Vitreoretinopathy (FEVR), is a new gene causing arRP with vitreous condensations supporting the evidence that this protein plays additional functions into the human retina.

}, keywords = {Amino Acid Sequence, Animals, Chlorocebus aethiops, Chromosome Mapping, COS Cells, DNA-Binding Proteins, Exome, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Molecular Sequence Data, Mutant Proteins, Pedigree, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Retinitis pigmentosa, Transcription Factors}, issn = {1460-2083}, doi = {10.1093/hmg/ddv140}, author = {Avila-Fernandez, Almudena and Perez-Carro, Raquel and Corton, Marta and Lopez-Molina, Maria Isabel and Campello, Laura and Garanto, Alejandro and Fernandez-Sanchez, Laura and Duijkers, Lonneke and Lopez-Martinez, Miguel Angel and Riveiro-Alvarez, Rosa and da Silva, Luciana Rodrigues Jacy and Sanchez-Alcudia, Roc{\'\i}o and Martin-Garrido, Esther and Reyes, Noelia and Garcia-Garcia, Francisco and Dopazo, Joaquin and Garcia-Sandoval, Blanca and Collin, Rob W J and Cuenca, Nicolas and Ayuso, Carmen} } @article {505, title = {Mammosphere formation in breast carcinoma cell lines depends upon expression of E-cadherin.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e77281}, abstract = {

Tumors are heterogeneous at the cellular level where the ability to maintain tumor growth resides in discrete cell populations. Floating sphere-forming assays are broadly used to test stem cell activity in tissues, tumors and cell lines. Spheroids are originated from a small population of cells with stem cell features able to grow in suspension culture and behaving as tumorigenic in mice. We tested the ability of eleven common breast cancer cell lines representing the major breast cancer subtypes to grow as mammospheres, measuring the ability to maintain cell viability upon serial non-adherent passage. Only MCF7, T47D, BT474, MDA-MB-436 and JIMT1 were successfully propagated as long-term mammosphere cultures, measured as the increase in the number of viable cells upon serial non-adherent passages. Other cell lines tested (SKBR3, MDA-MB-231, MDA-MB-468 and MDA-MB-435) formed cell clumps that can be disaggregated mechanically, but cell viability drops dramatically on their second passage. HCC1937 and HCC1569 cells formed typical mammospheres, although they could not be propagated as long-term mammosphere cultures. All the sphere forming lines but MDA-MB-436 express E-cadherin on their surface. Knock down of E-cadherin expression in MCF-7 cells abrogated its ability to grow as mammospheres, while re-expression of E-cadherin in SKBR3 cells allow them to form mammospheres. Therefore, the mammosphere assay is suitable to reveal stem like features in breast cancer cell lines that express E-cadherin.

}, keywords = {Breast Neoplasms, Cadherins, Cell Line, Tumor, Cell Proliferation, Cluster Analysis, Female, gene expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, MCF-7 Cells, Neoplastic Stem Cells, Spheroids, Cellular, Tumor Cells, Cultured}, issn = {1932-6203}, doi = {10.1371/journal.pone.0077281}, author = {Manuel Iglesias, Juan and Beloqui, Izaskun and Garcia-Garcia, Francisco and Leis, Olatz and Vazquez-Martin, Alejandro and Eguiara, Arrate and Cufi, Silvia and Pavon, Andres and Menendez, Javier A and Dopazo, Joaquin and Martin, Angel G} } @article {507, title = {Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome.}, journal = {Clin Chim Acta}, volume = {421}, year = {2013}, month = {2013 Jun 05}, pages = {184-90}, abstract = {

BACKGROUND: Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS.

METHODS AND RESULTS: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using a larger and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes were found to be differentially expressed in the first 48 h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study.

CONCLUSIONS: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.

}, keywords = {Acute Coronary Syndrome, Acute-Phase Proteins, Adult, biomarkers, Blood Cells, Early Diagnosis, gene expression, Gene Expression Profiling, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Transcriptome}, issn = {1873-3492}, doi = {10.1016/j.cca.2013.03.011}, author = {Silbiger, Vivian N and Luchessi, Andr{\'e} D and Hirata, Ros{\'a}rio D C and Lima-Neto, L{\'\i}dio G and Cavichioli, D{\'e}bora and Carracedo, {\'A}ngel and Bri{\'o}n, Maria and Dopazo, Joaquin and Garcia-Garcia, Francisco and Dos Santos, Elizabete S and Ramos, Rui F and Sampaio, Marcelo F and Armaganijan, Dikran and Sousa, Amanda G M R and Hirata, Mario H} } @article {501, title = {Role of CPI-17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film-forming medical device containing photolyase and UV filters.}, journal = {Exp Dermatol}, volume = {22}, year = {2013}, month = {2013 Jul}, pages = {494-6}, abstract = {

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6-4 photoproducts (6-4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film-forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over-expression of the CPI-17 gene, and a dependence on the initial expression level was observed (P~=~0.001). Low CPI-17 levels were directly associated with pro-inflammatory genes such as TNF (P~=~0.012) and IL-1B (P~=~0.07). Our results suggest a role for CPI-17 in restoring skin homoeostasis in CFC lesions.

}, keywords = {Administration, Topical, Adult, Aged, Aged, 80 and over, Biopsy, Deoxyribodipyrimidine Photo-Lyase, Female, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Homeostasis, Humans, Inflammation, Intracellular Signaling Peptides and Proteins, Liposomes, Male, Middle Aged, Muscle Proteins, Phenotype, Phosphoprotein Phosphatases, Reactive Oxygen Species, Skin, Skin Neoplasms, Ultraviolet Rays}, issn = {1600-0625}, doi = {10.1111/exd.12177}, author = {Puig-Butille, Joan Anton and Malvehy, Josep and Potrony, Miriam and Trullas, Carles and Garcia-Garcia, Francisco and Dopazo, Joaquin and Puig, Susana} } @article {516, title = {IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.}, journal = {Stem Cell Rev Rep}, volume = {8}, year = {2012}, month = {2012 Sep}, pages = {905-16}, abstract = {

Mesenchymal stem cells are often transplanted into inflammatory environments where they are able to survive and modulate host immune responses through a poorly understood mechanism. In this paper we analyzed the responses of MSC to IL-1β: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1β revealed that this cytokine activateds a set of genes related to biological processes such as cell survival, cell migration, cell adhesion, chemokine production, induction of angiogenesis and modulation of the immune response. Further more detailed analysis by real-time PCR and functional assays revealed that IL-1β mainly increaseds the production of chemokines such as CCL5, CCL20, CXCL1, CXCL3, CXCL5, CXCL6, CXCL10, CXCL11 and CX(3)CL1, interleukins IL-6, IL-8, IL23A, IL32, Toll-like receptors TLR2, TLR4, CLDN1, metalloproteins MMP1 and MMP3, growth factors CSF2 and TNF-α, together with adhesion molecules ICAM1 and ICAM4. Functional analysis of MSC proliferation, migration and adhesion to extracellular matrix components revealed that IL-1β did not affect proliferation but also served to induce the secretion of trophic factors and adhesion to ECM components such as collagen and laminin. IL-1β treatment enhanced the ability of MSC to recruit monocytes and granulocytes in vitro. Blockade of NF-κβ transcription factor activation with IκB kinase beta (IKKβ) shRNA impaired MSC migration, adhesion and leucocyte recruitment, induced by IL-1β demonstrating that NF-κB pathway is an important downstream regulator of these responses. These findings are relevant to understanding the biological responses of MSC to inflammatory environments.

}, keywords = {Cell Adhesion, Cell Movement, Cell Proliferation, Chemokines, Chemotaxis, Leukocyte, Collagen, Fibronectins, Gene Expression Profiling, Gene Knockdown Techniques, HEK293 Cells, Humans, I-kappa B Kinase, Inflammation Mediators, Intercellular Signaling Peptides and Proteins, Interleukin-1beta, Laminin, Leukocytes, Mesenchymal Stem Cells, NF-kappa B, Oligonucleotide Array Sequence Analysis, RNA Interference, Signal Transduction}, issn = {2629-3277}, doi = {10.1007/s12015-012-9364-9}, author = {Carrero, Rub{\'e}n and Cerrada, Inmaculada and Lled{\'o}, Elisa and Dopazo, Joaquin and Garcia-Garcia, Francisco and Rubio, Mari-Paz and Trigueros, C{\'e}sar and Dorronsoro, Akaitz and Ruiz-Sauri, Amparo and Montero, Jos{\'e} Anastasio and Sep{\'u}lveda, Pilar} } @article {590, title = {Direct functional assessment of the composite phenotype through multivariate projection strategies.}, journal = {Genomics}, volume = {92}, year = {2008}, month = {2008 Dec}, pages = {373-83}, abstract = {

We present a novel approach for the analysis of transcriptomics data that integrates functional annotation of gene sets with expression values in a multivariate fashion, and directly assesses the relation of functional features to a multivariate space of response phenotypical variables. Multivariate projection methods are used to obtain new correlated variables for a set of genes that share a given function. These new functional variables are then related to the response variables of interest. The analysis of the principal directions of the multivariate regression allows for the identification of gene function features correlated with the phenotype. Two different transcriptomics studies are used to illustrate the statistical and interpretative aspects of the methodology. We demonstrate the superiority of the proposed method over equivalent approaches.

}, keywords = {Breast Neoplasms, Computational Biology, Databases, Genetic, Female, Gene Expression Profiling, Humans, Mathematical Computing, Multivariate Analysis, Phenotype}, issn = {1089-8646}, doi = {10.1016/j.ygeno.2008.05.015}, author = {Conesa, Ana and Bro, Rasmus and Garcia-Garcia, Francisco and Prats, Jos{\'e} Manuel and G{\"o}tz, Stefan and Kjeldahl, Karin and Montaner, David and Dopazo, Joaquin} }