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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4627-4634. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-08-3115. This Article Full Text (PDF) All Versions of this Article: 2004-08-3115v1 105/12/4627    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flygare, J. Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Flygare, J. Articles by Karlsson, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 11, 2004 Accepted December 18, 2004 Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia Johan Flygare, Thomas Kiefer, Koichi Miyake, Taiju Utsugisawa, Isao Hamaguchi, Lydie Da Costa, Johan Richter, Edward J Davey, Hans Matsson, Niklas Dahl, Maciej Wiznerowicz, Didier Trono, and Stefan Karlsson* Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and The Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine and The Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden; Clinic for Internal Medicine C, Department of Hematology and Oncology, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan Hopital Bicetre, Le Kremlin-Bicetre, France Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University Hospital, Uppsala, Sweden Department of Genetics and Microbiology, University of Geneva, Geneva, Switzerland * Corresponding author; email: Stefan.karlsson{at}molmed.lu.se. Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia in which 25% of the patients have a mutation in the ribosomal protein S19 (RPS19) gene. In order to study effects of RPS19 deficiency in hematopoiesis we transduced CD34+ umbilical cord blood (CB) and bone marrow (BM) cells with three lentiviral vectors expressing siRNA against RPS19 and one scrambled control vector. All vectors also express GFP. Transduction with the siRNA vectors reduced RPS19 mRNA levels to various degrees, which resulted in erythroid defects, correlating to the degree of RPS19 downregulation and was rescued by expression of an siRNA-resistant RPS19 transcript. Erythroid colony formation capacity conjointly decreased with RPS19 levels in CD34+ CB and BM cells. In liquid culture supporting erythroid differentiation, RPS19-silenced as well as DBA patient CD34+ cells exhibited reduced proliferative capacity and impaired erythroid differentiation resulting in fewer CFU-Es. When assaying myeloid development a less pronounced influence on proliferation was seen. This study shows for the first time that RPS19 silencing decreases the proliferative capacity of hematopoietic progenitors and leads to a defect in erythroid development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: RPS19: pleads guilty in DBA case? Laure Coulombel Blood 2005 105: 4549-4550. [Full Text] [PDF] This article has been cited by other articles: S. Robledo, R. A. Idol, D. L. Crimmins, J. H. Ladenson, P. J. Mason, and M. Bessler The role of human ribosomal proteins in the maturation of rRNA and ribosome production RNA, September 1, 2008; 14(9): 1918 - 1929. [Abstract] [Full Text] [PDF] K. Miyake, T. Utsugisawa, J. Flygare, T. Kiefer, I. Hamaguchi, J. Richter, and S. Karlsson Ribosomal Protein S19 Deficiency Leads to Reduced Proliferation and Increased Apoptosis but Does Not Affect Terminal Erythroid Differentiation in a Cell Line Model of Diamond-Blackfan Anemia Stem Cells, February 1, 2008; 26(2): 323 - 329. [Abstract] [Full Text] [PDF] J. L. Moody, S. Singbrant, G. Karlsson, U. Blank, M. Aspling, J. Flygare, D. Bryder, and S. Karlsson Endoglin Is Not Critical for Hematopoietic Stem Cell Engraftment and Reconstitution but Regulates Adult Erythroid Development Stem Cells, November 1, 2007; 25(11): 2809 - 2819. [Abstract] [Full Text] [PDF] M. Angelini, S. Cannata, V. Mercaldo, L. Gibello, C. Santoro, I. Dianzani, and F. Loreni Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome Hum. Mol. Genet., July 15, 2007; 16(14): 1720 - 1727. [Abstract] [Full Text] [PDF] J. Flygare and S. Karlsson Diamond-Blackfan anemia: erythropoiesis lost in translation Blood, April 15, 2007; 109(8): 3152 - 3154. [Abstract] [Full Text] [PDF] S. Orru, A. Aspesi, M. Armiraglio, M. Caterino, F. Loreni, M. Ruoppolo, C. Santoro, and I. Dianzani Analysis of the Ribosomal Protein S19 Interactome Mol. Cell. Proteomics, March 1, 2007; 6(3): 382 - 393. [Abstract] [Full Text] [PDF] B. Y. Zhou, Z. Ye, G. Chen, Z. P. Gao, Y. A. Zhang, and L. Cheng Inducible and Reversible Transgene Expression in Human Stem Cells After Efficient and Stable Gene Transfer Stem Cells, March 1, 2007; 25(3): 779 - 789. [Abstract] [Full Text] [PDF] V. Choesmel, D. Bacqueville, J. Rouquette, J. Noaillac-Depeyre, S. Fribourg, A. Cretien, T. Leblanc, G. Tchernia, L. Da Costa, and P.-E. Gleizes Impaired ribosome biogenesis in Diamond-Blackfan anemia Blood, February 1, 2007; 109(3): 1275 - 1283. [Abstract] [Full Text] [PDF] H. T. Gazda, A. T. Kho, D. Sanoudou, J. M. Zaucha, I. S. Kohane, C. A. Sieff, and A. H. Beggs Defective Ribosomal Protein Gene Expression Alters Transcription, Translation, Apoptosis, and Oncogenic Pathways in Diamond-Blackfan Anemia Stem Cells, September 1, 2006; 24(9): 2034 - 2044. [Abstract] [Full Text] [PDF] M. W. Lensch and G. Q. Daley Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells Blood, April 1, 2006; 107(7): 2605 - 2612. [Abstract] [Full Text] [PDF] B. L. Ebert, M. M. Lee, J. L. Pretz, A. Subramanian, R. Mak, T. R. Golub, and C. A. Sieff An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray Blood, June 15, 2005; 105(12): 4620 - 4626. [Abstract] [Full Text] [PDF]

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