Differential Transcriptome of Tolerogenic Versus Inflammatory
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New Insights Into Epididymal Function in Relation to Sperm Maturation
REPRODUCTIONREVIEW New insights into epididymal function in relation to sperm maturation Jean-Louis Dacheux and Franc¸oise Dacheux UMR INRA-CNRS 7247, 37380 Nouzilly, France Correspondence should be addressed to J-L Dacheux; Email: [email protected] Abstract Testicular spermatozoa acquire fertility only after 1 or 2 weeks of transit through the epididymis. At the end of this several meters long epididymal tubule, the male gamete is able to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte to result in a viable embryo. All these sperm properties are acquired after sequential modifications occurring either at the level of the spermatozoon or in the epididymal surroundings. Over the last few decades, significant increases in the understanding of the composition of the male gamete and its surroundings have resulted from the use of new techniques such as genome sequencing, proteomics combined with high-sensitivity mass spectrometry, and gene-knockout approaches. This review reports and discusses the most relevant new results obtained in different species regarding the various cellular processes occurring at the sperm level, in particular, those related to the development of motility and egg binding during epididymal transit. Reproduction (2014) 147 R27–R42 Introduction sequentially throughout the epididymis. In view of these two parallel events, most investigations have The formation of fertile spermatozoa is the result of involved assessing the relationships between these two spectacular stages of cell differentiation that begin in events and identifying the epididymal signals able to the male gonad and finish in the female tract. The control spermatozoon fertility. -
Characterization of BRCA1-Deficient Premalignant Tissues and Cancers Identifies Plekha5 As a Tumor Metastasis Suppressor
ARTICLE https://doi.org/10.1038/s41467-020-18637-9 OPEN Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor Jianlin Liu1,2, Ragini Adhav1,2, Kai Miao1,2, Sek Man Su1,2, Lihua Mo1,2, Un In Chan1,2, Xin Zhang1,2, Jun Xu1,2, Jianjie Li1,2, Xiaodong Shu1,2, Jianming Zeng 1,2, Xu Zhang1,2, Xueying Lyu1,2, Lakhansing Pardeshi1,3, ✉ ✉ Kaeling Tan1,3, Heng Sun1,2, Koon Ho Wong 1,3, Chuxia Deng 1,2 & Xiaoling Xu 1,2 1234567890():,; Single-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intra- tumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing SNVs and CNVs simultaneously in bulk and single cells of premalignant tissues and tumors from mouse and human BRCA1-associated breast cancers, we discover an evolution process through which the tumors initiate from cells with SNVs affecting driver genes in the premalignant stage and malignantly progress later via CNVs acquired in chromosome regions with cancer driver genes. These events occur randomly and hit many putative cancer drivers besides p53 to generate unique genetic and pathological features for each tumor. Upon this, we finally identify a tumor metastasis suppressor Plekha5, whose deficiency promotes cancer metastasis to the liver and/or lung. 1 Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, China. 2 Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau, SAR, China. -
Immune Regulation by CD52-Expressing CD4 T Cells
Cellular & Molecular Immunology (2013) 10, 379–382 ß 2013 CSI and USTC. All rights reserved 1672-7681/13 $32.00 www.nature.com/cmi RESEARCH HIGHLIGHT Immune regulation by CD52-expressing CD4 T cells Ban-Hock Toh1, Tin Kyaw1,2, Peter Tipping1 and Alex Bobik2 T-cell regulation by CD52-expressing CD4 T cells appears to operate by two different and possibly synergistic mechanisms. The first is by its release from the cell surface of CD4 T cells that express high levels of CD52 that then binds to the inhibitory sialic acid-binding immunoglobulin-like lectins-10 (Siglec-10) receptor to attenuate effector T-cell activation by impairing phosphorylation of T-cell receptor associated lck and zap-70. The second mechanism appears to be by crosslinkage of the CD52 molecules by an as yet unidentified endogenous ligand that is mimicked by a bivalent anti-CD52 antibody that results in their expansion. Cellular & Molecular Immunology (2013) 10, 379–382; doi:10.1038/cmi.2013.35; published online 12 August 2013 he immune system is designed to appears in the affirmative, and includes suppression was lost by cleavage of N- T protect its host from invading players such as IL-10-secreting Tr1 and glycans from CD52-Fc by peptide N- pathogens and yet remain non-reactive TGF-b-secreting Th3. cells. Absence of glycosidase or by removal of sialic acid to self. Immunological homeostasis is surface markers limited the usefulness residues by neuraminidase. Suppression maintained by purging self-reactive lym- of these other regulators. However, the was also blocked by antibody to the phocytes by clonal deletion coupled with recent report that CD49b and lympho- extracellular domain of Siglec-10 and a regulatory population of lymphocytes cyte activation gene-3 are highly and sta- by soluble Siglec-10-Fc. -
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. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Mutation of Plekha7 Attenuates Salt-Sensitive Hypertension in the Rat
Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat Bradley T. Endresa,b, Jessica R. C. Priestleya, Oleg Palygina, Michael J. Flistera,b, Matthew J. Hoffmana, Brian D. Weinberga, Michael Grzybowskia,b, Julian H. Lombarda, Alexander Staruschenkoa, Carol Morenoa,b, Howard J. Jacoba,b,c, and Aron M. Geurtsa,b,d,1 Departments of aPhysiology and cPediatrics, bHuman and Molecular Genetics Center, and dCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226 Edited by Richard P. Lifton, Yale University School of Medicine, New Haven, CT, and approved July 23, 2014 (received for review June 24, 2014) PLEKHA7 (pleckstrin homology domain containing family A mem- hypertension and renal injury by selective ablation of adaptive im- em1Mcwi em1Mcwi ber 7) has been found in multiple studies as a candidate gene for mune cells in the SS-Rag1 and SS-Cd247 knockout human hypertension, yet functional data supporting this associa- rats (16, 17) and reduced hypertension and renal injury in the em1Mcwi tion are lacking. We investigated the contribution of this gene SS-Ncf2 (p67phox) null model exhibiting reduced medul- to the pathogenesis of salt-sensitive hypertension by mutating lary oxidative stress (18). Additionally, we have recently demon- Plekha7 in the Dahl salt-sensitive (SS/JrHsdMcwi) rat using zinc- strated multiple genes at a single hypertension GWAS-nominated finger nuclease technology. After four weeks on an 8% NaCl diet, locus (Agtrap-Plod1 locus) can have additive or subtractive effects homozygous mutant rats had lower mean arterial (149 ± 9 mmHg on blood pressure and renal function when mutated in the SS rat vs. -
Constitutive Expression of Murine Ctla4ig from a Recombinant Adenovirus Vector Results in Prolonged Transgene Expression
Gene Therapy (1997) 4, 853–860 1997 Stockton Press All rights reserved 0969-7128/97 $12.00 Constitutive expression of murine CTLA4Ig from a recombinant adenovirus vector results in prolonged transgene expression DB Schowalter1, L Meuse1, CB Wilson2,3, PS Linsley4 and MA Kay1,2,5,6 1Division of Medical Genetics, Department of Medicine, and Departments of 2Pediatrics, 3Immunology, 6Biochemistry and 5Pathology, University of Washington; and 4Bristol-Myers Squibb Pharmaceuticals, Seattle, WA, USA The administration of soluble muCTLA4Ig around the time Ad.RSV-muCTLA4Ig and a reporter adenovirus (2 × 109 of adenovirus vector mediated gene transfer into murine p.f.u. of Ad.PGK-hAAT) resulted in prolonged reporter hepatocytes has been shown to markedly prolong trans- gene expression, reduced anti-adenovirus and anti-hAAT gene expression, diminish the formation of adenovirus antibody production, and attenuated T cell proliferation and neutralizing antibody, decrease T cell proliferative IFN-g production in response to adenoviral vector. Mice response and infiltration into the liver without causing irre- given a constant total amount of adenovirus with dimin- versible systemic immunosuppression. In this study, an ishing amounts of Ad.RSV-muCTLA4Ig and a constant E1/E3-deleted adenovirus vector constitutively expressing amount of reporter virus (2 × 109 p.f.u. of Ad.PGK-hAAT) murine CTLA4Ig (Ad.RSV-muCTLA4Ig) was constructed in demonstrated prolonged reporter gene expression and order to determine if production of muCTLA4Ig from within decreased anti-adenovirus and anti-hAAT antibody pro- transduced cells (ie hepatocytes) would provide a more duction only when high serum levels of muCTLA4Ig were specific/localized interference with the CD28/B7–1 and produced. -
A Novel Raji-Burkitt's Lymphoma Model for Preclinical and Mechanistic Evaluation of CD52-Targeted Immunotherapeutic Agents
Cancer Therapy: Preclinical A Novel Raji-Burkitt’s Lymphoma Model for Preclinical and Mechanistic Evaluation of CD52-Targeted Immunotherapeutic Agents Rosa Lapalombella,1Xiaobin Zhao,1, 2 Georgia Triantafillou,1Bo Yu,3,4 Yan Jin, 4 Gerard Lozanski,5 Carolyn Cheney,1Nyla Heerema,5 David Jarjoura,6 Amy Lehman,6 L. James Lee,3,4 Guido Marcucci,1Robert J. Lee,2,4 Michael A. Caligiuri,1 Natarajan Muthusamy,1and John C. Byrd1, 2 Abstract Purpose:Todate, efforts to study CD52-targeted therapies, such as alemtuzumab, have beenlim- ited due to the lack of stable CD52 expressing transformed B-cell lines and animal models.We describe generation and utilization of cell lines that stably express CD52 both in vitro and in vivo. Experimental Design: By limiting dilution, we have established several clones of Raji-Burkitt’s lymphoma cell line that express surface CD52. Immunophenotype and cytogenetic charac- terizationof these clones was done. In vivo usefulness of the CD52high cell line to evaluate the ther- apeuticefficacyofCD52-directedantibody wasinvestigatedusingaSCIDmousexenograftmodel. Results: Stable expression of CD52 was confirmed in cells cultured in vitro up to 52 weeks of continuous growth. The functional integrity of the expressed CD52 molecule was shown using alemtuzumab, which induced cytotoxic effects in vitro in the CD52high but not the CD52low clone. Compared with control antibody, alemtuzumab treatment in CD52high inoculated mice resulted in significantly increased median survival. Comparable levels of CD52-targeted direct cyto- toxicity, complement-dependent cytotoxicity, and antibody-dependent cytotoxicity and anti-CD52 immunoliposome-mediated delivery of synthetic oligodeoxyribo nucleotides in CD52high clone and primary B-chronic lymphocytic leukemia cells implicated potential in vivo application of this model for evaluation of CD52-targeted antibody and immunoliposomes encapsulating therapeutic agents. -
In Antithymocyte and Antilymphocyte Globulin: Possible Role for the Expansion of GPI-AP Deficient Cells in Aplastic Anemia Heike H
Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia Heike H. Breitinger, Markus T. Rojewski, Hubert Schrezenmeier To cite this version: Heike H. Breitinger, Markus T. Rojewski, Hubert Schrezenmeier. Antibodies to glycosylphosphatidyl- inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia. Annals of Hematology, Springer Verlag, 2009, 88 (9), pp.889-895. 10.1007/s00277-008-0688-0. hal-00535024 HAL Id: hal-00535024 https://hal.archives-ouvertes.fr/hal-00535024 Submitted on 11 Nov 2010 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. Ann Hematol (2009) 88:889–895 DOI 10.1007/s00277-008-0688-0 ORIGINAL ARTICLE Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia Heike H. Breitinger & Markus T. Rojewski & Hubert Schrezenmeier Received: 19 September 2008 /Accepted: 18 December 2008 /Published online: 13 January 2009 # Springer-Verlag 2009 Abstract Antithymocyte globulin (ATG) and antilymphocyte immunosuppressive effects in treatment of aplastic anemia. -
Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications
Stem Cell Rev and Rep DOI 10.1007/s12015-016-9662-8 Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications Behnam Ahmadian Baghbaderani 1 & Adhikarla Syama2 & Renuka Sivapatham3 & Ying Pei4 & Odity Mukherjee2 & Thomas Fellner1 & Xianmin Zeng3,4 & Mahendra S. Rao5,6 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract We have recently described manufacturing of hu- help determine which set of tests will be most useful in mon- man induced pluripotent stem cells (iPSC) master cell banks itoring the cells and establishing criteria for discarding a line. (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Keywords Induced pluripotent stem cells . Embryonic stem Reports, 5(4), 647–659, 2015). In this manuscript, we de- cells . Manufacturing . cGMP . Consent . Markers scribe the detailed characterization of the two iPSC clones generated using this process, including whole genome se- quencing (WGS), microarray, and comparative genomic hy- Introduction bridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibra- Induced pluripotent stem cells (iPSCs) are akin to embryonic tion material and with a reporter subclone and lines made by a stem cells (ESC) [2] in their developmental potential, but dif- similar process from different donors. We believe that iPSCs fer from ESC in the starting cell used and the requirement of a are likely to be used to make multiple clinical products. We set of proteins to induce pluripotency [3]. Although function- further believe that the lines used as input material will be used ally identical, iPSCs may differ from ESC in subtle ways, at different sites and, given their immortal status, will be used including in their epigenetic profile, exposure to the environ- for many years or even decades. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in