DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,029,992 B2 Rapko Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,029,992 B2 Rapko Et Al USO08029992B2 (12) United States Patent (10) Patent No.: US 8,029,992 B2 Rapko et al. (45) Date of Patent: Oct. 4, 2011 (54) METHODS OF EVALUATING CELLS AND guishes chondrocytes from Synovial cells. Tissue Engineering. Part CELL CULTURES C. Methods, vol. 16, No. 6, pp. 1367-1375, Dec. 2010.* Appendix A of Real-Time PCR Systems: Applied Biosystems (75) Inventors: Stephen M. Rapko, Franklin, MA (US); 7900HT Fast Real-Time PCR System and 7300/7500 Real-Time Stephen J. Duguay, Salem, MA (US) PCR Systems, Chemistry Guide, Applied Biosystems, 2005, Part No. 4348358 Rev. E. pp. A1-A4. Applied Biosystems, "Amplification Efficiency of TaqMan(R) Gene (73) Assignee: Genzyme Corporation, Cambridge, MA Expression Assays”. Application Note TaqMan(R) Gene Expression (US) Assays, Publication 127AP05-03 (2006), printed as pp. 1-6. Applied Biosystems, Taq Man R Gene Expression Assays, ASSay ID (*) Notice: Subject to any disclaimer, the term of this Hs00157103 ml, retrieved online at https://products.ap patent is extended or adjusted under 35 pliedbiosystems.com on Oct. 30, 2006, printed as pp. 1-3. U.S.C. 154(b) by 559 days. Applied Biosystems, Taq Man R Gene Expression Assays, ASSay ID Hs00185803 ml, retrieved online at https://products.ap (21) Appl. No.: 12/098,033 pliedbiosystems.com on Oct. 30, 2006, printed as pp. 1-3. Basad, et al. Treatment of Chondral Defects by Matrix-Guided (22) Filed: Apr. 4, 2008 Autologous Chondrocyte Implantation (MACI), in Cartilage Sur gery and Future Perspectives 50-56 (2003). (65) Prior Publication Data Benya, et al., “Dedifferentiated Chondrocytes Rexpress the Differ entiated Collagen Phenotype When Cultured in Agarose Gels”. Cell, US 2008/02484.81 A1 Oct. 9, 2008 30:215-224 (1982). Binette, et al., “Expression of a Stable Articular Cartilage Phenotype Related U.S. Application Data without Evidence of Hypertrophy by Adult Human Articular Chondrocytes. In Vitro”, Jour: of Orthopaed Research., 16:207-216 (60) Provisional application No. 60/910,574, filed on Apr. (1998). 6, 2007. Brittberg et al., “Treatment of Deep Cartilage Defects in the Knee with Autologous ChondrocyteTransplantation'. N.E.J. of Medicine, (51) Int. Cl. 331;889-895 (1994). CI2O I/68 (2006.01) Brittberg, M., “Autologous Chondrocyte Transplantation'. Clin. CI2O 1/02 (2006.01) Orthopaedics and Related Research, 367S:S147-155 (1999). CI2P 19/34 (2006.01) Buckwalter, et al., “The Effect of Link Protein on Proteoglycan GOIN33/53 (2006.01) Aggregate Structure'. Jour: of Biological Chem., 259(9):5361-5363 (1984). (52) U.S. Cl. ............... 435/6: 435/29: 435/91.2: 435/7.1 Cherubino, et al., “Autologous chondrocyte implantation using a (58) Field of Classification Search ........................ None bilayer collagen membrane: A preliminary report. Jour: of See application file for complete search history. Orthopaedic Surgery, 11(1):10-15 (2003). Galbraith, et al., “Global analysis of cell type-specific gene expres (56) References Cited sion'. Comparative and Functional Genomics, 4:208-215 (2003). U.S. PATENT DOCUMENTS (Continued) 6,150,163 A 11/2000 McPherson et al. 7,169,610 B2 1/2007 Brown 2003/0087259 A1* 5/2003 Clancy et al. ..................... 435/6 Primary Examiner — Jennifer Dunston 2007/0292949 A1 12/2007 Duguay (74) Attorney, Agent, or Firm — Finnegan, Henderson, Farabow, Garrett & Dunner, LLP FOREIGN PATENT DOCUMENTS WO WO 2006/094836 A2 9, 2006 WO WO 2007 149328 12/2007 (57) ABSTRACT OTHER PUBLICATIONS Methods of evaluating the composition of a cell culture (e.g., Pusztai and Hess. Clinical trial design for microarray predictive to distinguish chondrocytes from fibroblasts) and methods for marker discovery and assessment. Annals of Oncology, vol. 15, pp. evaluating the phenotype of an individual cell (e.g., as a 1731-1737, 2004.* chondrocyte) are disclosed. The methods may be used, for Golub et al. Molecular classification of cancer: Class discovery and example, for assessing chondrocyte cultures used for treat class prediction by gene expression monitoring. Science, vol. 286, ment of cartilage defects. In some embodiments, the inven pp. 531-537, Oct. 1999.* tion involves identifying cell culture composition or the iden Tan et al. Classification analysis of the transcriptosome of tity of a cell based on expression level of a fibroblast marker. nonlesional cultured dermal fibroblasts from systemic sclerosis In other embodiments, the invention involves comparing patients with early disease. Arthitis & Rhematism, vol. 52, No. 3, pp. expression levels of at least one chondrocyte marker and at 865-876, Mar. 2005.* Entrez Gene entry for MFAP5 microfibrillar associated protein 5 least one fibroblast marker in a cell culture sample or in an Homo sapiens). Gene ID: 8076, updated on Nov. 1, 2010, printed as individual cell. In illustrative embodiments, the chondrocyte pp. 1-5 on Nov. 9, 2010.* marker is hyaluronan and proteoglycan link protein 1 Entrez Gene entry for HAPLN1 hyaluronan and proteoglycan link (HAPLN1), and the fibroblast marker is microfibrillar asso protein 1 Homo sapiens. Gene ID: 1404, updated on Nov. 1, 2010, ciated protein 5 (MFAP5). printed as pp. 1-6 on Nov. 9, 2010.* Rapko et al. Identification of the chondrocyte lineage using microfibril-associated glycoprotein-2, a novel marker that distin 34 Claims, 18 Drawing Sheets US 8,029.992 B2 Page 2 OTHER PUBLICATIONS Gibson, et al., “Microfibril-associated Glycoprotein-2 (MAGP-2) Is GenBank Accession No. NM 000095, “Homo sapiens cartilage Specifically Associated with Fibrillin-containing Microfibrils but Exhibits More Restricted Patterns of Tissue Localization and Devel oliomeric matrix protein (COMP), mRNA'. Dec. 2003. opmental Expression Than Its Structural Relative MAGP-1”,Jour: of GenBank Accession No. NM 000346, "Homo sapiens SRY (Sex Histochem. & Cytochem., 46(8):871-885 (1998). determining region Y)-box 9 (campomelic dysplasia, autosomal sex Haudenschild, et al., “Differential Expression of Multiple Genes reversal) (SOX9), mRNA'. Jul. 2005. During Articular Chondrocyte Redifferentiation'. The Anatomical GenBank Accession No. NM 000900, “Homo sapiens matrix Gla Record, 263:91-98 (2001). protein (MGP), mRNA'. Feb. 2006. Imabayashi, et al., “Redifferentiation of dedifferentiated GenBank Accession No. NM 00101 1705, "Homo sapiens chondrocytes and chondrogenesis of human bone marrow Stromal leukocyte cell derived chemotaxin 1 (LECT1), transcript variant 2, cells via chondrosphereformation with expression profiling by large mRNA'. Aug. 2006. scale cDNA analysis”. Experimental Cell Research, 288:35-50 GenBank Accession No. NM 001135, "Homo sapiens aggrecan 1, (2003). transcript variant 1, mRNA'. Oct. 2004. Lemaire, et al., “Increased Expression of Type I Collagen Induced by GenBank Accession No. NM 001844. "Homo sapiens collagen, Microfibril-Associated Glycoprotein 2'. Arthritis & Rheumatism, type II, alpha I (COL2A1), transcript variant 1, mRNA'. Apr. 2003. 52: 1812-1823 (2005). GenBank Accession No. NM 001851, “Homo sapiens collagen, Lemaire, et al., “Mutant Fibrillin 1 From tight Skin Mice Increases type IX, alpha 1 (COL9A1), transcript variant 1, mRNA'. Oct. 2006. Extracellular Matrix Incorporation of Microfibril-Associated GenBank Accession No. NM 001854, "Homo sapiens collagen, Glycoprotein 2 and type I Collagen'. Arthritis & Rheumatism, type XI, alpha 1 (COL11A1), transcript variant A, mRNA'. Sep. 50(3):915-926 (2004). 2006. Leung, et al., “Fundametnals of cDNA microarray data analysis'. GenBank Accession No. NM 001884. "Homo sapiens hyaluronan TRENDS in Genetics, 19(11):649-659 (2003). and proteoglycan link protein 1 (HAPLN1)”, Oct. 2005. Linsenmeyer et al., “Monoclonal Antibodies to Connective Tissue GenBank Accession No. NM 003880, “Homo sapiens WNT1 Macromolecules: Type II Collagen'. Biochem. Biophys. Res. Com., inducible signaling pathway protein 3 (WISP3), transcript variant 1, 92(2):440-6 (1980). mRNA'. Aug. 2006. Marlovits, et al., “Early postoperative adherence of matrix-induced GenBank Accession No. NM 005711. "Homo sapiens EGF-like autologous chondrocyte implantation for the treatment of full-thick repeats and discoidin I-like domains 3 (EDIL3), mRNA'. Oct. 2005. ness cartilage defects of the femoral condyle'. Knee Surg. Sports GenBank Accession No. NM 006272, "Homo sapiens S100 cal Traumatol Arthrosc. 12:451-457 (2005). cium binding protein, beta (neural) (S100B), mRN”. Aug. 2005. Rapko, et al., “DNA Methylation Analysis as Novel Tool for Quality GenBank Accession No. NM 006393, "Homo sapiens nebulette Control in Regenerative Medicine”. Tissue Engineering, 13(9):2271 (NEBL), transcript variant 1 mRNA'. Apr. 2008. 2280 (2007). GenBank Accession No. NM 007015, "Homo sapiens leukocyte Reno et al., “Rapid Isolation of Total RNA from Small Samples of cell derived chemotaxin 1 (LECT1), transcript variant 1, mRNA'. Hypocellular, Dense Connective Tissues'. Biotechniques, Apr. 2005. 22(6):1082-1086 (1997). GenBank Accession No. NM 013227. “Homo sapiens aggrecan 1 International Search Report issued in PCT/US2008/059275, mailed (AGC1), transcript variant 2, mRNA'. Oct. 2004. on Aug. 5, 2008. GenBank Accession No. NM 018058, “Homo sapiens cartilage Written Opinion issued in PCT/US2008/059275, mailed on Aug. 5, acidic protein 1 (CRTAC1), mRNA'. Sep. 2005. 2008. GenBank Accession No. NM 033150, “Homo sapiens collagen, Kolettas, E. et al. “Expression of cartilage-specific molecules is type II, alpha 1 (COL2A1), transcript variant 2, mRNA'. Apr. 2003. retained on long-term culture of human articular chondrocytes' J. GenBank Accession No. NM 078485. “Homo sapiens collagen,
Load more

Recommended publications
  • Versican V2 Assembles the Extracellular Matrix Surrounding the Nodes of Ranvier in the CNS
    The Journal of Neuroscience, June 17, 2009 • 29(24):7731–7742 • 7731 Cellular/Molecular Versican V2 Assembles the Extracellular Matrix Surrounding the Nodes of Ranvier in the CNS María T. Dours-Zimmermann,1 Konrad Maurer,2 Uwe Rauch,3 Wilhelm Stoffel,4 Reinhard Fa¨ssler,5 and Dieter R. Zimmermann1 Institutes of 1Surgical Pathology and 2Anesthesiology, University Hospital Zurich, CH-8091 Zurich, Switzerland, 3Vascular Wall Biology, Department of Experimental Medical Science, University of Lund, S-221 00 Lund, Sweden, 4Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany, and 5Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany The CNS-restricted versican splice-variant V2 is a large chondroitin sulfate proteoglycan incorporated in the extracellular matrix sur- rounding myelinated fibers and particularly accumulating at nodes of Ranvier. In vitro, it is a potent inhibitor of axonal growth and therefore considered to participate in the reduction of structural plasticity connected to myelination. To study the role of versican V2 during postnatal development, we designed a novel isoform-specific gene inactivation approach circumventing early embryonic lethality of the complete knock-out and preventing compensation by the remaining versican splice variants. These mice are viable and fertile; however, they display major molecular alterations at the nodes of Ranvier. While the clustering of nodal sodium channels and paranodal structures appear in versican V2-deficient mice unaffected, the formation of the extracellular matrix surrounding the nodes is largely impaired. The conjoint loss of tenascin-R and phosphacan from the perinodal matrix provide strong evidence that versican V2, possibly controlled by a nodal receptor, organizes the extracellular matrix assembly in vivo.
    [Show full text]
  • Kids First Pediatric Research Program (Kids First) Poster Session at ASHG Accelerating Pediatric Genomics Research Through Collaboration October 15Th, 2019
    The Gabriella Miller Kids First Pediatric Research Program (Kids First) Poster Session at ASHG Accelerating Pediatric Genomics Research through Collaboration October 15th, 2019 Background The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans- NIH Common Fund program initiated in response to the 2014 Gabriella Miller Kids First Research Act. The program’s vision is to alleviate suffering from childhood cancer and structural birth defects by fostering collaborative research to uncover the etiology of these diseases and support data sharing within the pediatric research community. This is implemented through developing the Gabriella Miller Kids First Data Resource (Kids First Data Resource) and populating this resource with whole genome sequence datasets and associated clinical and phenotypic information. Both childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions. Purpose During this evening poster session, attendees will gain a broad understanding of the utility of the genomic data generated by Kids First, learn about the progress of Kids First X01 cohort projects, and observe demonstrations of the tools and functionalities of the recently launched Kids First Data Resource Portal. The session is an opportunity for the scientific community and public to engage with Kids First investigators, collaborators, and a growing community of researchers, patient foundations, and families. Several other NIH and external data efforts will present posters and be available to discuss collaboration opportunities as we work together to accelerate pediatric research.
    [Show full text]
  • H4K16 Acetylation Marks Active Genes and Enhancers of Embryonic Stem Cells, but Does Not Alter Chromatin Compaction
    Downloaded from genome.cshlp.org on October 5, 2021 - Published by Cold Spring Harbor Laboratory Press H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction Gillian Taylor1, Ragnhild Eskeland2, Betül Hekimoglu-Balkan1, Madapura M. Pradeepa1* and Wendy A Bickmore1* 1 MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK 2Current address: Department of Molecular Biosciences, University of Oslo, N-0316 Oslo, Norway *Correspondence to: W. Bickmore or M.M. Pradeepa, MRC Human Genetics Unit, MRC IGMM, Crewe Road, Edinburgh EH4 2XU, UK Tel: +44 131 332 2471 Fax: +44 131 467 8456 Email:[email protected] or [email protected] Running head: H4K16 acetylation and long-range genome regulation Keywords: Chromatin compaction, embryonic stem cells, fluorescence in situ hybridization, histone acetylation, long-range regulation, 1 Downloaded from genome.cshlp.org on October 5, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract Compared with histone H3, acetylation of H4 tails has not been well studied, especially in mammalian cells. Yet, H4K16 acetylation is of particular interest because of its ability to decompact nucleosomes in vitro and its involvement in dosage compensation in flies. Here we show that, surprisingly, loss of H4K16 acetylation does not alter higher-order chromatin compaction in vivo in mouse embryonic stem cells (ESCs). As well as peaks of acetylated H4K16 and Kat8/MOF histone acetyltransferase at the transcription start sites of expressed genes, we report that acetylation of H4K16 is a new marker of active enhancers in ESCs and that some enhancers are marked by H3K4me1, Kat8 and H4K16ac but not by acetylated H3K27 or p300/EP300, suggesting that they are novel EP300 independent regulatory elements.
    [Show full text]
  • A Single-Cell Transcriptomic Landscape of Primate Arterial Aging
    ARTICLE https://doi.org/10.1038/s41467-020-15997-0 OPEN A single-cell transcriptomic landscape of primate arterial aging Weiqi Zhang 1,2,3,4,5,13, Shu Zhang6,7,13, Pengze Yan3,8,13, Jie Ren7,9,13, Moshi Song3,5,8, Jingyi Li2,3,8, Jinghui Lei4, Huize Pan2,3, Si Wang3,5,8, Xibo Ma3,10, Shuai Ma2,3,8, Hongyu Li2,3, Fei Sun2,3, Haifeng Wan3,5,11, ✉ ✉ ✉ Wei Li 3,5,11, Piu Chan4, Qi Zhou3,5,11, Guang-Hui Liu 2,3,4,5,8 , Fuchou Tang 6,7,9,12 & Jing Qu 3,5,11 Our understanding of how aging affects the cellular and molecular components of the vas- 1234567890():,; culature and contributes to cardiovascular diseases is still limited. Here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize tran- scriptional landmarks that regulate vascular senility and position FOXO3A, a longevity- associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders. 1 CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • Agonists and Knockdown of Estrogen Receptor Β Differentially Affect
    Schüler-Toprak et al. BMC Cancer (2016) 16:951 DOI 10.1186/s12885-016-2973-y RESEARCH ARTICLE Open Access Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro Susanne Schüler-Toprak1*, Julia Häring1, Elisabeth C. Inwald1, Christoph Moehle2, Olaf Ortmann1 and Oliver Treeck1 Abstract Background: Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines. Methods: MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software. Results: Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism.
    [Show full text]
  • Distinct Genetic Alterations in Colorectal Cancer
    Distinct Genetic Alterations in Colorectal Cancer Hassan Ashktorab1*, Alejandro A. Scha¨ffer2, Mohammad Daremipouran3, Duane T. Smoot3, Edward Lee3, Hassan Brim3 1 Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America, 2 National Center for Biotechnology Information, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, United States of America, 3 Department of Pathology, Howard University, College of Medicine, Washington, DC, United States of America Abstract Background: Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. Methodology/Principal Findings: We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. Conclusions/Significance: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs.
    [Show full text]
  • Key Genes Regulating Skeletal Muscle Development and Growth in Farm Animals
    animals Review Key Genes Regulating Skeletal Muscle Development and Growth in Farm Animals Mohammadreza Mohammadabadi 1 , Farhad Bordbar 1,* , Just Jensen 2 , Min Du 3 and Wei Guo 4 1 Department of Animal Science, Faculty of Agriculture, Shahid Bahonar University of Kerman, Kerman 77951, Iran; [email protected] 2 Center for Quantitative Genetics and Genomics, Aarhus University, 8210 Aarhus, Denmark; [email protected] 3 Washington Center for Muscle Biology, Department of Animal Sciences, Washington State University, Pullman, WA 99163, USA; [email protected] 4 Muscle Biology and Animal Biologics, Animal and Dairy Science, University of Wisconsin-Madison, Madison, WI 53558, USA; [email protected] * Correspondence: [email protected] Simple Summary: Skeletal muscle mass is an important economic trait, and muscle development and growth is a crucial factor to supply enough meat for human consumption. Thus, understanding (candidate) genes regulating skeletal muscle development is crucial for understanding molecular genetic regulation of muscle growth and can be benefit the meat industry toward the goal of in- creasing meat yields. During the past years, significant progress has been made for understanding these mechanisms, and thus, we decided to write a comprehensive review covering regulators and (candidate) genes crucial for muscle development and growth in farm animals. Detection of these genes and factors increases our understanding of muscle growth and development and is a great help for breeders to satisfy demands for meat production on a global scale. Citation: Mohammadabadi, M.; Abstract: Farm-animal species play crucial roles in satisfying demands for meat on a global scale, Bordbar, F.; Jensen, J.; Du, M.; Guo, W.
    [Show full text]
  • Endothelial Perspective on Tumor Development
    www.oncotarget.com Oncotarget, 2020, Vol. 11, (No. 36), pp: 3387-3404 Research Paper Down syndrome iPSC model: endothelial perspective on tumor development Mariana Perepitchka1,2, Yekaterina Galat1,2,3,*, Igor P. Beletsky3, Philip M. Iannaccone1,2,4,5 and Vasiliy Galat2,3,4,5,6 1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 2Developmental Biology Program, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, USA 3Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 5Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA 6ARTEC Biotech Inc, Chicago, IL, USA *Co-first author Correspondence to: Mariana Perepitchka, email: [email protected] Yekaterina Galat, email: [email protected] Vasiliy Galat, email: [email protected] Keywords: Down syndrome; iPSC-derived endothelial model; T21 genome-wide Implications; meta-analysis; tumor microenvironment Received: July 10, 2019 Accepted: August 01, 2020 Published: September 08, 2020 Copyright: Perepitchka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Trisomy 21 (T21), known as Down syndrome (DS), is a widely studied chromosomal abnormality. Previous studies have shown that DS individuals have a unique cancer profile. While exhibiting low solid tumor prevalence, DS patients are at risk for hematologic cancers, such as acute megakaryocytic leukemia and acute lymphoblastic leukemia.
    [Show full text]
  • Perineuronal Nets and Metal Cation Concentrations in The
    biomolecules Review Perineuronal Nets and Metal Cation Concentrations in the Microenvironments of Fast-Spiking, Parvalbumin-Expressing GABAergic Interneurons: Relevance to Neurodevelopment and Neurodevelopmental Disorders Jessica A. Burket 1, Jason D. Webb 1 and Stephen I. Deutsch 2,* 1 Department of Molecular Biology & Chemistry, Christopher Newport University, Newport News, VA 23606, USA; [email protected] (J.A.B.); [email protected] (J.D.W.) 2 Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 710, Norfolk, VA 23507, USA * Correspondence: [email protected]; Tel.: +1-757-446-5888 Abstract: Because of their abilities to catalyze generation of toxic free radical species, free concen- trations of the redox reactive metals iron and copper are highly regulated. Importantly, desired neurobiological effects of these redox reactive metal cations occur within very narrow ranges of their local concentrations. For example, synaptic release of free copper acts locally to modulate NMDA receptor-mediated neurotransmission. Moreover, within the developing brain, iron is criti- cal to hippocampal maturation and the differentiation of parvalbumin-expressing neurons, whose soma and dendrites are surrounded by perineuronal nets (PNNs). The PNNs are a specialized Citation: Burket, J.A.; Webb, J.D.; component of brain extracellular matrix, whose polyanionic character supports the fast-spiking elec- Deutsch, S.I. Perineuronal Nets and trophysiological properties of these parvalbumin-expressing GABAergic interneurons. In addition Metal Cation Concentrations in the to binding cations and creation of the Donnan equilibrium that support the fast-spiking properties Microenvironments of Fast-Spiking, of this subset of interneurons, the complex architecture of PNNs also binds metal cations, which Parvalbumin-Expressing GABAergic may serve a protective function against oxidative damage, especially of these fast-spiking neurons.
    [Show full text]
  • Rna-Sequencing Applications: Gene Expression Quantification and Methylator Phenotype Identification
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2013 RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION Guoshuai Cai Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Computational Biology Commons, and the Medicine and Health Sciences Commons Recommended Citation Cai, Guoshuai, "RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION" (2013). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 386. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/386 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION
    [Show full text]
  • Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection
    fgene-11-00358 April 9, 2020 Time: 15:55 # 1 ORIGINAL RESEARCH published: 15 April 2020 doi: 10.3389/fgene.2020.00358 Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection Allen F. Ryan1*, Chanond A. Nasamran2, Kwang Pak1, Clara Draf1, Kathleen M. Fisch2, Nicholas Webster3 and Arwa Kurabi1 1 Departments of Surgery/Otolaryngology, UC San Diego School of Medicine, VA Medical Center, La Jolla, CA, United States, 2 Medicine/Center for Computational Biology & Bioinformatics, UC San Diego School of Medicine, VA Medical Center, La Jolla, CA, United States, 3 Medicine/Endocrinology, UC San Diego School of Medicine, VA Medical Center, La Jolla, CA, United States Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, Edited by: two endothelial, one pericyte and one melanocyte cluster. Within some clusters, Amélie Bonnefond, Institut National de la Santé et de la cell subtypes were identified. While many corresponded to those cell types known Recherche Médicale (INSERM), from prior studies, several novel types or subtypes were noted. The results indicate France unexpected cellular diversity within the resting middle ear mucosa. The resolution of Reviewed by: Fabien Delahaye, uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major Institut Pasteur de Lille, France role. Thus innate immunity is likely responsible for normal recovery from middle ear Nelson L. S. Tang, infection. The need for rapid response to pathogens suggests that innate immune The Chinese University of Hong Kong, China genes may be constitutively expressed by middle ear cells.
    [Show full text]