DOCSLIB.ORG

Evidence for an Early Endometrial Response to Pregnancy in Cattle: Both Dependent Upon and Independent of Interferon Tau N

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau N. Forde, G.B. Duffy, P.A. Mcgettigan, J.A. Browne, J.P. Mehta, A.K. Kelly, N. Mansouri-Attia, Olivier Sandra, B.J. Loftus, M.A. Crowe, et al. To cite this version: N. Forde, G.B. Duffy, P.A. Mcgettigan, J.A. Browne, J.P. Mehta, et al.. Evidence for an early en- dometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiological Genomics, American Physiological Society, 2012, 44 (16), pp.799-810. 10.1152/physi- olgenomics.00067.2012. hal-01000912 HAL Id: hal-01000912 https://hal.archives-ouvertes.fr/hal-01000912 Submitted on 29 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau N. Forde, G. B. Duffy, P. A. McGettigan, J. A. Browne, J. P. Mehta, A. K. Kelly, N. Mansouri-Attia, O. Sandra, B. J. Loftus, M. A. Crowe, T. Fair, J. F. Roche, P. Lonergan and A. C. O. Evans Downloaded from Physiol. Genomics 44:799-810, 2012. First published 3 July 2012; doi: 10.1152/physiolgenomics.00067.2012 You might find this additional info useful... Supplementary material for this article can be found at: http://physiolgenomics.physiology.org/ http://physiolgenomics.physiology.org/http://physiolgenomics.physiology.org/content/suppl/2012/0 7/06/physiolgenomics.00067.2012.DC1.html This article cites 55 articles, 36 of which you can access for free at: http://physiolgenomics.physiology.org/content/44/16/799.full#ref-list-1 Updated information and services including high resolution figures, can be found at: http://physiolgenomics.physiology.org/content/44/16/799.full Additional material and information about Physiological Genomics can be found at: http://www.the-aps.org/publications/physiolgenomics This information is current as of January 4, 2013. at INRA Institut National de la Recherche Agronomique on January 4, 2013 Physiological Genomics publishes results of a wide variety of studies from human and from informative model systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published 24 times a year (twice monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2012 the American Physiological Society. ESSN: 1531-2267. Visit our website at http://www.the-aps.org/. Physiol Genomics 44: 799–810, 2012. First published July 3, 2012; doi:10.1152/physiolgenomics.00067.2012. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau 1 1 1 1 3 1 1 N. Forde, G. B. Duffy, P. A. McGettigan, J. A. Browne, J. P. Mehta, A. K. Kelly, N. Mansouri-Attia, Downloaded from O. Sandra,4 B. J. Loftus,3 M. A. Crowe,2,3 T. Fair,1 J. F. Roche,2 P. Lonergan,1,3 and A. C. O. Evans1,3 1School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland; 2School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland; 3Conway Institute, University College Dublin, Belfield, Dublin, Ireland; 4Institut National de la Recherche Agronomique, Unite Mixté de Recherche, 1198 Biologie du Développement et Reproduction, Jouy en Josas, France Submitted 22 May 2012; accepted in final form 27 June 2012 http://physiolgenomics.physiology.org/ Forde N, Duffy GB, McGettigan PA, Browne JA, Mehta JP, Kelly nancy recognition signal in both cattle and sheep is interferon AK, Mansouri-Attia N, Sandra O, Loftus BJ, Crowe MA, Fair T, tau (IFNT) and in cattle, pregnancy recognition must occur by Roche JF, Lonergan P, Evans ACO. Evidence for an early endometrial day 16 to ensure luteolysis does not occur (6, 36). IFNT exerts response to pregnancy in cattle: both dependent upon and independent of its effects both locally on the uterus as well as in a paracrine interferon tau. Physiol Genomics 44: 799–810, 2012. First published July fashion on extra uterine tissues. A number of studies have 3, 2012; doi:10.1152/physiolgenomics.00067.2012.—The aims of this study were to 1) identify the earliest transcriptional response of the demonstrated that IFNT alters the transcriptome of the endo- bovine endometrium to the presence of the conceptus (using metrium during early pregnancy to increase expression of RNAseq), 2) investigate if these genes are regulated by interferon tau genes and/or transporters that enhance conceptus elongation (IFNT) in vivo, and 3) determine if they are predictive of the and to establish uterine receptivity to implantation (reviewed pregnancy status of postpartum dairy cows. RNAseq identified 459 by Ref. 46). These studies have shown that IFNT during the differentially expressed genes (DEGs) between pregnant and cyclic peri-implantation period of pregnancy in cattle induces the endometria on day 16. Quantitative real-time PCR analysis of selected expression of large numbers of interferon-stimulated genes at INRA Institut National de la Recherche Agronomique on January 4, 2013 genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and (ISGs; Refs. 3, 14, 19, 26, 31, 52). Indeed, the transcriptional DDX58 expression increased in pregnant compared with cyclic endo- response of the endometrium to the developing conceptus can metria on day 16 and were directly upregulated by intrauterine Ͻ act as a sensor of the developmental competency of the infusion of IFNT in vivo for2h(P 0.05). On day 13 following conceptus (5, 32). However, the majority of these studies have estrous endometrial expression of nine genes increased [ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, focused on the peri-implantation period of pregnancy during or ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven after the period of pregnancy recognition in cattle (3, 14, 26, genes decreased (SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, 31, 52). MGC128929, and WBSCR17; P Ͻ 0.05) in pregnant compared with Recent studies by our group and others sought to identify the cyclic heifers. Of these DEGs, significant differences in expression differences between the endometrial transcriptome of pregnant between pregnant and cyclic endometria were maintained on day 16 and cyclic heifers at distinct developmental stages of embryo for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, development. According to the Affymetrix microarray plat- and ZSWIM4 (P Ͻ 0.05) both their expression was not directly form the first detectable differences between the endometria of regulated by IFNT in vivo. Analysis of the expression of selected pregnant and cyclic heifers occurred on day 15 (4) and 16 (14). interferon-stimulated genes in blood samples from postpartum dairy Ͻ Despite this, interaction between the conceptus and the mater- cows revealed a significant increase (P 0.05) in expression of nal environment is required during the preimplantation stages ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared of pregnancy in cattle (45), and it is known that the bovine with cyclic controls. In conclusion, RNAseq identified a number of embryo expresses mRNA for IFNT as early as the blastocyst novel pregnancy-associated genes in the endometrium of cattle during stage of development (27, 29), indicating that the embryo may early pregnancy that are not regulated by IFNT in vivo. In addition, a elicit localized or subtle responses from the endometrium prior number of genes that are directly regulated by short term exposure to to pregnancy recognition. In addition, transcriptomic profiling IFNT in vivo are differentially expressed on day 18 following estrus of bovine embryos at the initiation of conceptus elongation detection in the blood of postpartum dairy cows depending on their (11) as well as trophoblast cells cultured in vitro (12, 50) pregnancy status. identified the expression of genes that code for secreted pro- RNA sequencing; uterine; gene expression; estrus cycle; interferon- teins. It is therefore reasonable to hypothesize that these stimulated gene conceptus-derived factors may stimulate more understated, localized gene expression changes in the endometrium during early pregnancy that are independent of IFNT. IN ORDER FOR SUCCESSFUL PREGNANCY to be established and Next-generation sequencing methods such as RNA sequenc- maintained in cattle, the corpus luteum (CL) must be main- ing (RNAseq) provide a far more precise measure of transcript tained beyond the time when luteolysis would normally occur. abundance than other methods developed to date; as it is It has been well established that the conceptus-derived preg- unbiased (no prior knowledge required), allowing complete coverage (i.e., very high sensitivity) and allowing true genome- Address for reprint requests and other correspondence: N. Forde, Veterinary wide discovery (33, 34). Data from human studies comparing Sciences Centre, Univ. College Dublin, Belfield, Dublin 4, Ireland (e-mail: the use of RNAseq and Affymetrix microarrays were highly [email protected]). correlated; however, the findings suggested that RNAseq was 1094-8341/12 Copyright © 2012 the American Physiological Society 799 800 EARLY RESPONSE OF THE BOVINE ENDOMETRIUM TO PREGNANCY the more sensitive of the two methods as it identified 30% more West Sussex, UK). RNA quality and quantity were determined with differentially expressed genes (DEGs) than the microarray the Agilent Bioanalyzer (Agilent Technologies, Santa Clara, CA), and platform, as validated by quantitative real-time PCR (qPCR) only samples with an RNA integrity number (RIN) of Ͼ8.5 were ϭ (33).
Recommended publications
  • Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

    Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

    Author Manuscript Published OnlineFirst on November 9, 2017; DOI: 10.1158/0008-5472.CAN-17-0946 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Deficiency in protein tyrosine phosphatase PTP1B shortens lifespan and leads to development of acute leukemia Samantha Le Sommer1, Nicola Morrice1, Martina Pesaresi1, Dawn Thompson1, Mark A. Vickers1, Graeme I. Murray1, Nimesh Mody1, Benjamin G Neel2, Kendra K Bence3,4, Heather M Wilson1*, & Mirela Delibegovic1* 1Institute of Medical Sciences, University of Aberdeen, United Kingdom 2Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York University, New York, New York 10016, USA. 3 Dept. of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, USA. 4 Current address: Internal Medicine Research Unit (IMRU), Pfizer Inc, 610 Main St. Cambridge, MA 02139 USA *corresponding authors: Prof. Mirela Delibegovic ([email protected]) and Dr. Heather Wilson ([email protected] ) Running Title: PTP1B deficiency shortens lifespan and leads to leukaemia Key Words: PTP1B, lifespan, leukaemia, myeloid, STAT3 Additional information: This work was performed with the funds from the Wellcome Trust ISSF grant to M. Delibegovic and BHF project grant to M. Delibegovic (PG/11/8/28703). S. Le Sommer is a recipient of the University of Aberdeen Institute of Medical Sciences PhD studentship. Conflict of interest: Authors declare there are no conflicts of interests. Word Count: 5,000 Figure Count: 6 Figures, 1 Table (Supplemental Figures: 6, Supplemental Tables: 4) 1 Downloaded from cancerres.aacrjournals.org on September 29, 2021. © 2017 American Association for Cancer Research.
  • Progesterone Receptor Membrane Component 1 Promotes Survival of Human Breast Cancer Cells and the Growth of Xenograft Tumors

    Progesterone Receptor Membrane Component 1 Promotes Survival of Human Breast Cancer Cells and the Growth of Xenograft Tumors

    Cancer Biology & Therapy ISSN: 1538-4047 (Print) 1555-8576 (Online) Journal homepage: http://www.tandfonline.com/loi/kcbt20 Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors Nicole C. Clark, Anne M. Friel, Cindy A. Pru, Ling Zhang, Toshi Shioda, Bo R. Rueda, John J. Peluso & James K. Pru To cite this article: Nicole C. Clark, Anne M. Friel, Cindy A. Pru, Ling Zhang, Toshi Shioda, Bo R. Rueda, John J. Peluso & James K. Pru (2016) Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors, Cancer Biology & Therapy, 17:3, 262-271, DOI: 10.1080/15384047.2016.1139240 To link to this article: http://dx.doi.org/10.1080/15384047.2016.1139240 Accepted author version posted online: 19 Jan 2016. Published online: 19 Jan 2016. Submit your article to this journal Article views: 49 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=kcbt20 Download by: [University of Connecticut] Date: 26 May 2016, At: 11:28 CANCER BIOLOGY & THERAPY 2016, VOL. 17, NO. 3, 262–271 http://dx.doi.org/10.1080/15384047.2016.1139240 RESEARCH PAPER Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors Nicole C. Clarka,*, Anne M. Frielb,*, Cindy A. Prua, Ling Zhangb, Toshi Shiodac, Bo R. Ruedab, John J. Pelusod, and James K. Prua aDepartment of Animal Sciences,
  • Environmental Influences on Endothelial Gene Expression

    Environmental Influences on Endothelial Gene Expression

    ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community.
  • Expanding the Genetic Basis of Copy Number Variation in Familial Breast

    Expanding the Genetic Basis of Copy Number Variation in Familial Breast

    Masson et al. Hereditary Cancer in Clinical Practice 2014, 12:15 http://www.hccpjournal.com/content/12/1/15 RESEARCH Open Access Expanding the genetic basis of copy number variation in familial breast cancer Amy L Masson1,4, Bente A Talseth-Palmer1,4, Tiffany-Jane Evans1,4, Desma M Grice1,2, Garry N Hannan2 and Rodney J Scott1,3,4* Abstract Introduction: Familial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades a number of genes have been identified that are unequivocally associated with breast cancer (BC) risk but there remain a significant proportion of families that cannot be accounted for by these genes. Copy number variants (CNVs) are a form of genetic variation yet to be fully explored for their contribution to fBC. CNVs exert their effects by either being associated with whole or partial gene deletions or duplications and by interrupting epigenetic patterning thereby contributing to disease development. CNV analysis can also be used to identify new genes and loci which may be associated with disease risk. Methods: The Affymetrix Cytogenetic Whole Genome 2.7 M (Cyto2.7 M) arrays were used to detect regions of genomic re-arrangement in a cohort of 129 fBC BRCA1/BRCA2 mutation negative patients with a young age of diagnosis (<50 years) compared to 40 unaffected healthy controls (>55 years of age). Results: CNV analysis revealed the presence of 275 unique rearrangements that were not present in the control population suggestive of their involvement in BC risk.
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
  • Expression of Progesterone Receptor Membrane Component 1, Serpine Mrna Binding Protein 1 and Nuclear Progesterone Receptor Isoforms a and B in the Bovine Myometrium During The

    Expression of Progesterone Receptor Membrane Component 1, Serpine Mrna Binding Protein 1 and Nuclear Progesterone Receptor Isoforms a and B in the Bovine Myometrium During The

    Journal of Reproduction and Development, Vol. 58, No 3, 2012 —Original Article— Expression of Progesterone Receptor Membrane Component 1, Serpine mRNA Binding Protein 1 and Nuclear Progesterone Receptor Isoforms A and B in the Bovine Myometrium During the Estrous Cycle and Early Pregnancy Dominika SLOnina1), Magdalena K. KOWALik1) and Jan KOTWica1) 1)Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland Abstract. The aim of this study was to investigate the (1) expression of progesterone membrane component 1 (PGRMC1), serpine mRNA binding protein 1 (SERBP1) and progesterone receptor (PR) mRNA and (2) protein expression levels of PGRMC1, SERBP1 and PR isoforms A and B in the bovine myometrium during the estrous cycle and early pregnancy. Uteri from cows on days 1–5, 6–10, 11–16 and 17–21 of the estrous cycle and weeks 3–5, 6–8 and 9–12 of pregnancy were used (n=5–6 per period). There were no changes (P>0.05) in PGRMC1 mRNA expression during the estrous cycle, while expression of SERBP1 and PR mRNA was the lowest (P<0.05) on days 11–16 relative to other days of the cycle. The highest mRNA expression of PGRMC1, SERBP1 and PR was found during pregnancy. There were no changes (P>0.05) in SERBP1 protein expression in cycling and pregnant cows, while the highest (P<0.05) PGRMC1 protein expression was found during weeks 3–5 of pregnancy. Similar protein expression profiles for PRA and PRB were found, and protein levels were highest on days 1–5 of the estrous cycle.
  • S41467-020-18249-3.Pdf

    S41467-020-18249-3.Pdf

    ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible.
  • Macropinocytosis Requires Gal-3 in a Subset of Patient-Derived Glioblastoma Stem Cells

    Macropinocytosis Requires Gal-3 in a Subset of Patient-Derived Glioblastoma Stem Cells

    ARTICLE https://doi.org/10.1038/s42003-021-02258-z OPEN Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells Laetitia Seguin1,8, Soline Odouard2,8, Francesca Corlazzoli 2,8, Sarah Al Haddad2, Laurine Moindrot2, Marta Calvo Tardón3, Mayra Yebra4, Alexey Koval5, Eliana Marinari2, Viviane Bes3, Alexandre Guérin 6, Mathilde Allard2, Sten Ilmjärv6, Vladimir L. Katanaev 5, Paul R. Walker3, Karl-Heinz Krause6, Valérie Dutoit2, ✉ Jann N. Sarkaria 7, Pierre-Yves Dietrich2 & Érika Cosset 2 Recently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glio- 1234567890():,; blastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3- mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macro- pinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of- principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients. 1 University Côte d’Azur, CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging (IRCAN), Nice, France. 2 Laboratory of Tumor Immunology, Department of Oncology, Center for Translational Research in Onco-Hematology, Swiss Cancer Center Léman (SCCL), Geneva University Hospitals, University of Geneva, Geneva, Switzerland.
  • Transcriptome-Wide Profiling of Cerebral Cavernous Malformations

    Transcriptome-Wide Profiling of Cerebral Cavernous Malformations

    www.nature.com/scientificreports OPEN Transcriptome-wide Profling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures Santhilal Subhash 2,8, Norman Kalmbach3, Florian Wegner4, Susanne Petri4, Torsten Glomb5, Oliver Dittrich-Breiholz5, Caiquan Huang1, Kiran Kumar Bali6, Wolfram S. Kunz7, Amir Samii1, Helmut Bertalanfy1, Chandrasekhar Kanduri2* & Souvik Kar1,8* Cerebral cavernous malformations (CCMs) are low-fow vascular malformations in the brain associated with recurrent hemorrhage and seizures. The current treatment of CCMs relies solely on surgical intervention. Henceforth, alternative non-invasive therapies are urgently needed to help prevent subsequent hemorrhagic episodes. Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identifcation in CCMs pathology remains unknown. The objective of the current study was to identify lncRNAs associated with CCMs pathogenesis using patient cohorts having 10 CCM patients and 4 controls from brain. Executing next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identifed 1,967 lncRNAs and 4,928 protein coding genes (PCGs) to be diferentially expressed in CCMs patients. Among these, we selected top 6 diferentially expressed lncRNAs each having signifcant correlative expression with more than 100 diferentially expressed PCGs. The diferential expression status of the top lncRNAs, SMIM25 and LBX2-AS1 in CCMs was further confrmed by qRT-PCR analysis. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology.
  • The RNA-Binding Protein SERBP1 Functions As a Novel Oncogenic

    The RNA-Binding Protein SERBP1 Functions As a Novel Oncogenic

    Kosti et al. Genome Biology (2020) 21:195 https://doi.org/10.1186/s13059-020-02115-y RESEARCH Open Access The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation Adam Kosti1,2†, Patricia Rosa de Araujo1,2†, Wei-Qing Li1,3†, Gabriela D. A. Guardia4†, Jennifer Chiou5†, Caihong Yi1, Debashish Ray6, Fabiana Meliso4, Yi-Ming Li3, Talia Delambre1, Mei Qiao1, Suzanne S. Burns1ˆ, Franziska K. Lorbeer1, Fanny Georgi1, Markus Flosbach1, Sarah Klinnert1, Anne Jenseit1, Xiufen Lei1, Carolina Romero Sandoval1, Kevin Ha6, Hong Zheng6, Renu Pandey1, Aleksandra Gruslova7, Yogesh K. Gupta1, Andrew Brenner8, Erzsebet Kokovay2, Timothy R. Hughes6,9,10, Quaid D. Morris6,9,11, Pedro A. F. Galante4*, Stefano Tiziani5* and Luiz O. F. Penalva1,2* * Correspondence: pgalante@ mochsl.org.br; [email protected]. Abstract edu; [email protected] ˆSuzanne S. Burns is deceased. Background: RNA-binding proteins (RBPs) function as master regulators of gene 4Centro de Oncologia Molecular, expression. Alterations in RBP expression and function are often observed in cancer Hospital Sírio-Libanês, São Paulo, and influence critical pathways implicated in tumor initiation and growth. São Paulo 01309-060, Brazil 5Department of Nutritional Identification and characterization of oncogenic RBPs and their regulatory networks Sciences, Dell Pediatric Research provide new opportunities for targeted therapy. Institute, Dell Medical School, The University of Texas at Austin, Austin, Results: We identify the RNA-binding protein SERBP1 as a novel regulator of TX 78712, USA glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and 1Children’s Cancer Research correlates with poor patient survival and poor response to chemo- and radiotherapy.
  • Gene-Based and Pathway-Based Genome-Wide Association Study of Alcohol Dependence

    Gene-Based and Pathway-Based Genome-Wide Association Study of Alcohol Dependence

    • 111 • Shanghai Archives of Psychiatry, 2015, Vol. 27, No. 2 •Original research article• Gene-based and pathway-based genome-wide association study of alcohol dependence Lingjun ZUO1, Clarence K. ZHANG2,3*, Frederick G. SAYWARD4,5, Kei-Hoi CHEUNG4, Kesheng WANG6, John H. KRYSTAL1, Hongyu ZHAO2, Xingguang LUO1* Background: The organization of risk genes within signaling pathways may provide clues about the converging neurobiological effects of risk genes for alcohol dependence. Aims: Identify risk genes and risk gene pathways for alcohol dependence. Methods: We conducted a pathway-based genome-wide association study (GWAS) of alcohol dependence using a gene-set-rich analytic approach. Approximately one million genetic markers were tested in the discovery sample which included 1409 European-American (EA) alcohol dependent individuals and 1518 EA healthy comparison subjects. An additional 681 African-American (AA) cases and 508 AA healthy subjects served as the replication sample. Results: We identified several genome-wide replicable risk genes and risk pathways that were significantly associated with alcohol dependence. After applying the Bonferroni correction for multiple testing, the ‘cell- extracellular matrix interactions’ pathway (p<2.0E-4 in EAs) and the PXN gene (which encodes paxillin) (p=3.9E-7 in EAs) within this pathway were the most promising risk factors for alcohol dependence. There were also two nominally replicable pathways enriched in alcohol dependence-related genes in both EAs (0.015≤p≤0.035) and AAs (0.025≤p≤0.050): the ‘Na+/Cl- dependent neurotransmitter transporters’ pathway and the ‘other glycan degradation’ pathway. Conclusions: These findings provide new evidence highlighting several genes and biological signaling processes that may be related to the risk for alcohol dependence.
  • Alzheimer's Disease

    Alzheimer's Disease

    VU Research Portal Spot the difference Bossers, C.A.M. 2009 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Bossers, C. A. M. (2009). Spot the difference: microarray analysis of gene expression changes in Alzheimer's and Parkinson's Disease. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 11. Oct. 2021 Spot the difference: microarray analysis of gene expression changes in Alzheimer’s and Parkinson’s Disease The research described in this thesis was conducted at the Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sci- ences, Amsterdam, The Netherlands. The research was financially supported by a collaboration between the Netherlands Institute for Neuroscience and Solvay Phar- maceuticals. Leescommissie: dr.