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Deficiency of ribos...
Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia
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- Flygare, Johan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Kiefer, Thomas (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Miyake, Koichi (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Utsugisawa, Taiju (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Hamaguchi, Isao (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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Da Costa, Lydie (author)
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- Richter, Johan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Davey, Edward J (author)
- Uppsala universitet,Institutionen för genetik och patologi,Research Group of Clinical Molecular Genetics
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- Matsson, Hans (author)
- Uppsala universitet,Institutionen för genetik och patologi,Research Group of Clinical Molecular Genetics
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- Dahl, Niklas (author)
- Uppsala universitet,Institutionen för genetik och patologi,Research Group of Clinical Molecular Genetics
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Wiznerowicz, Maciej (author)
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Trono, Didier (author)
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- Karlsson, Stefan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- American Society of Hematology, 2005
- 2005
- English.
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 105:12, s. 4627-4634
- Related links:
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http://www.ncbi.nlm....
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
Close
- 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. To study effects of RPS19 deficiency in hematopoiesis we transduced CD34+ umbilical cord blood (CB) and bone marrow (BM) cells with 3 lentiviral vectors expressing small interfering RNA (siRNA) against RPS19 and 1 scrambled control vector. All vectors also express green fluorescent protein (GFP). Transduction with the siRNA vectors reduced RPS19 mRNA levels to various degrees, which resulted in erythroid defects, correlating to the degree of RPS19 down-regulation, 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 erythroid colony-forming units (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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Anemia; Diamond-Blackfan/*blood/pathology
- Antigens; CD/biosynthesis
- Antigens; CD34/*biosynthesis
- Antigens; Differentiation; B-Lymphocyte/biosynthesis
- Base Sequence
- Blotting; Northern
- Blotting; Western
- Bone Marrow Cells/cytology
- Cell Differentiation
- Cell Line
- Cell Proliferation
- Cell Separation
- Cloning; Molecular
- Down-Regulation
- Erythroid Progenitor Cells/metabolism
- Flow Cytometry
- Gene Silencing
- Genetic Vectors
- Green Fluorescent Proteins/chemistry/metabolism
- Hematopoiesis
- Humans
- Image Processing; Computer-Assisted
- Lentivirus/genetics
- Molecular Sequence Data
- Phenotype
- RNA; Messenger/metabolism
- RNA; Small Interfering/*metabolism
- Receptors; Transferrin
- Reverse Transcriptase Polymerase Chain Reaction
- Ribosomal Proteins/*deficiency/*physiology
- Ribosomes/metabolism
- Time Factors
- Transgenes
- Umbilical Cord/cytology
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
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Blood
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
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Flygare, Johan
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Kiefer, Thomas
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Miyake, Koichi
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Utsugisawa, Taij ...
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Hamaguchi, Isao
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Da Costa, Lydie
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show more...
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Richter, Johan
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Davey, Edward J
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Matsson, Hans
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Dahl, Niklas
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Wiznerowicz, Mac ...
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Trono, Didier
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Karlsson, Stefan
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Blood
- By the university
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Uppsala University
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Lund University