A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice.

  • Thai T
  • Calado D
  • Casola S
 et al. 
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Abstract

Clinically successful hematopoietic cell transplantation is dependent on hematopoietic stem and progenitor cells. Here we identify the matricellular protein Nephroblastoma Overexpressed (Nov, CCN3) as being essential for their functional integrity. Nov expression is restricted to the primitive (CD34) compartments of umbilical vein cord blood, and its knockdown in these cells by lentivirus-mediated RNA interference abrogates their function in vitro and in vivo. Conversely, forced expression of Nov and addition of recombinant Nov protein both enhance primitive stem and/or progenitor activity. Taken together, our results identify Nov (CCN3) as a regulator of human hematopoietic stem or progenitor cells.

Author-supplied keywords

  • 14
  • 2005
  • 3' Untranslated Regions
  • 3' Untranslated Regions: analysis
  • 3' Untranslated Regions: genetics
  • 3' Untranslated Regions: metabolism
  • 3T3 Cells
  • 5' Untranslated Regions
  • AMP-Activated Protein Kinases
  • Amino Acid Sequence
  • Amino Acids
  • Amino Acids: metabolism
  • Angiogenic Proteins
  • Angiogenic Proteins: genetics
  • Animal
  • Animal: immunology
  • Animals
  • Antibodies
  • Antigens
  • Antisense
  • Antisense: genetics
  • Antisense: metabolism
  • Antisense: pharmacology
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Apoptosis Regulatory Proteins: metabolism
  • Apoptosis: genetics
  • B-Cell
  • B-Cell: genetics
  • B-Cell: pathology
  • B-Lymphocytes
  • B-Lymphocytes: cytology
  • B-Lymphocytes: immunology
  • BH3 Interacting Domain Death Agonist Protein
  • BH3 Interacting Domain Death Agonist Protein: meta
  • Base Sequence
  • Binding Sites
  • Binding Sites: genetics
  • Biological
  • Blood Cells
  • Blood Cells: metabolism
  • Blood Chemical Analysis
  • Blotting
  • Bone Marrow Cells
  • Bone Marrow Cells: cytology
  • Breast
  • Breast Neoplasms
  • Breast Neoplasms: genetics
  • Breast Neoplasms: metabolism
  • Breast Neoplasms: pathology
  • Breast: metabolism
  • CCAAT-Enhancer-Binding Proteins
  • CCAAT-Enhancer-Binding Proteins: genetics
  • CD34
  • CD34: analysis
  • CD34: immunology
  • CD4-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes: cytology
  • CD4-Positive T-Lymphocytes: virology
  • Cell Cycle
  • Cell Cycle: genetics
  • Cell Cycle: physiology
  • Cell Death
  • Cell Death: genetics
  • Cell Differentiation
  • Cell Differentiation: immunology
  • Cell Differentiation: physiology
  • Cell Hypoxia
  • Cell Hypoxia: genetics
  • Cell Line
  • Cell Movement
  • Cell Movement: physiology
  • Cell Proliferation
  • Cell Transformation
  • Cells
  • Cholesterol
  • Cholesterol: biosynthesis
  • Cholesterol: blood
  • Cholesterol: metabolism
  • Chromatography
  • Colony-Forming Units Assay
  • Comparative Genomic Hybridization
  • Complementary
  • Complementary: administration & dosage
  • Complementary: genetics
  • Complementary: metabolism
  • Complementary: pharmacology
  • Computational Biology
  • Connective Tissue Growth Factor
  • Conserved Sequence
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factor Alpha 2 Subunit: genetics
  • Core Binding Factor Alpha 2 Subunit: metabolism
  • Core Binding Factor Alpha 2 Subunit: physiology
  • Cultured
  • Cytochromes c
  • Cytochromes c: secretion
  • Cytokine
  • Cytokine: metabolism
  • Cytokines
  • Cytokines: biosynthesis
  • DEAD-box RNA Helicases
  • DEAD-box RNA Helicases: genetics
  • DEAD-box RNA Helicases: metabolism
  • DNA
  • DNA Primers
  • DNA Transposable Elements
  • DNA Transposable Elements: genetics
  • DNA-Binding Proteins
  • DNA-Binding Proteins: metabolism
  • DNA: metabolism
  • Dendritic Cells
  • Dendritic Cells: cytology
  • Dendritic Cells: immunology
  • Developmental
  • Diffuse
  • Diffuse: genetics
  • Diffuse: pathology
  • Disease Models
  • Disease-Free Survival
  • Down-Regulation
  • Down-Regulation: drug effects
  • E2F Transcription Factors
  • E2F Transcription Factors: genetics
  • E2F Transcription Factors: metabolism
  • Embryonic Stem Cells
  • Embryonic Stem Cells: cytology
  • Embryonic Stem Cells: metabolism
  • Endoribonucleases
  • Endoribonucleases: genetics
  • Endoribonucleases: metabolism
  • Enzyme Activation
  • Enzyme Activation: drug effects
  • Enzymologic
  • Enzymologic: genetics
  • Epistasis
  • Erythroid Cells
  • Erythroid Cells: cytology
  • Erythroid Cells: metabolism
  • Eukaryotic Initiation Factor-2
  • Evolution
  • Exons
  • Exons: genetics
  • Experimental
  • Experimental: genetics
  • Experimental: virology
  • Expressed Sequence Tags
  • Factor IX
  • Factor IX: administration & dosage
  • Factor IX: immunology
  • Fatty Acids
  • Fatty Acids: metabolism
  • Feedback
  • Female
  • Fetus
  • Fetus: cytology
  • Fetus: immunology
  • Forkhead Transcription Factors
  • Forkhead Transcription Factors: biosynthesis
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression Regulation: drug effects
  • Gene Expression Regulation: physiology
  • Gene Silencing
  • Gene Silencing: drug effects
  • Gene Targeting
  • Gene Transfer Techniques
  • Genes
  • Genes: genetics
  • Genetic
  • Genetic Therapy
  • Genetic Therapy: methods
  • Genetic Vectors
  • Genetic Vectors: therapeutic use
  • Genetic: genetics
  • Genome
  • Germinal Center
  • Germinal Center: immunology
  • Granulocyte-Macrophage Colony-Stimulati
  • HIV-1
  • HIV-1: physiology
  • HL-60 Cells
  • HeLa Cells
  • Hematopoiesis
  • Hematopoiesis: genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Hematopoietic Stem Cells: cytology
  • Hematopoietic Stem Cells: immunology
  • Hematopoietic Stem Cells: metabolism
  • Hematopoietic Stem Cells: physiology
  • Hemophilia B
  • Hemophilia B: therapy
  • Heterologous
  • High Pressure Liquid
  • Homeostasis
  • Humans
  • Immediate-Early Proteins
  • Immediate-Early Proteins: genetics
  • Immediate-Early Proteins: physiology
  • Immune System
  • Immune System: physiology
  • Immunoglobulin
  • Immunoglobulin G
  • Immunoglobulin G: analysis
  • Immunoglobulin G: biosynthesis
  • Immunologic
  • Immunologic: genetics
  • Immunologic: metabolism
  • Immunological
  • Immunoprecipitation
  • In Situ Hybridization
  • Inbred BALB C
  • Inbred NOD
  • Inflammation
  • Intercellular Signaling Peptides and Proteins
  • Intercellular Signaling Peptides and Proteins: gen
  • Intercellular Signaling Peptides and Proteins: phy
  • Interferon-beta
  • Interferon-beta: metabolism
  • Inverted Repeat Sequences
  • Inverted Repeat Sequences: genetics
  • Islets of Langerhans
  • Islets of Langerhans: cytology
  • Islets of Langerhans: embryology
  • Islets of Langerhans: metabolism
  • K562 Cells
  • Killer Cells
  • Kinetics
  • Knockout
  • Large B-Cell
  • Lentivirus
  • Lentivirus: genetics
  • Leukemia
  • Leukemia Virus
  • Lipid Metabolism
  • Lipid Metabolism: physiology
  • Liver
  • Liver: cytology
  • Liver: embryology
  • Liver: immunology
  • Liver: metabolism
  • Lung
  • Lung Diseases
  • Lung Diseases: immunology
  • Lung Diseases: pathology
  • Lung: pathology
  • Lymphocyte Activation
  • Lymphoma
  • Lymphopoiesis
  • Lymphotoxin-alpha
  • Lymphotoxin-alpha: biosynthesis
  • Lymphotoxin-beta
  • Lymphotoxin-beta: biosynthesis
  • Macrophage Colony-Stimulating Factor
  • Macrophage Colony-Stimulating Factor: bi
  • Macrophages
  • Macrophages: immunology
  • Macrophages: metabolism
  • Male
  • Mammals
  • Mammals: genetics
  • Megakaryocytes
  • Megakaryocytes: cytology
  • Membrane Glycoproteins
  • Membrane Glycoproteins: genetics
  • Membrane Glycoproteins: metabolism
  • Membrane Proteins
  • Membrane Proteins: metabolism
  • Messenger
  • Messenger: analysis
  • Messenger: genetics
  • Messenger: metabolism
  • Methylation
  • Mice
  • MicroRNAs
  • MicroRNAs: analysis
  • MicroRNAs: antagonists & inhibitors
  • MicroRNAs: biosynthesis
  • MicroRNAs: chemistry
  • MicroRNAs: classification
  • MicroRNAs: genetics
  • MicroRNAs: isolation & purification
  • MicroRNAs: metabolism
  • MicroRNAs: pharmacology
  • MicroRNAs: physiology
  • Microarray Analysis
  • Mitochondria
  • Mitochondria: metabolism
  • Mitochondria: secretion
  • Models
  • Molecular
  • Molecular Sequence Data
  • Monocytes
  • Monocytes: cytology
  • Monocytes: metabolism
  • Morphogenesis
  • Morphogenesis: physiology
  • Multienzyme Complexes
  • Multienzyme Complexes: metabolism
  • Multigene Family
  • Multigene Family: genetics
  • Murine
  • Murine: genetics
  • Mutation
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Myeloid Cells
  • Myeloid Cells: cytology
  • Myelopoiesis
  • NIH 3T3 Cells
  • Natural
  • Natural: cytology
  • Natural: immunology
  • Neoplasm
  • Neoplasm Proteins
  • Neoplasm Proteins: genetics
  • Neoplasm Proteins: metabolism
  • Neoplasm: metabolism
  • Neoplasms
  • Neoplasms: genetics
  • Neoplasms: metabolism
  • Neoplasms: pathology
  • Neoplastic
  • Neovascularization
  • Nephroblastoma Overexpressed Protein
  • Nitrophenols
  • Nitrophenols: immunology
  • Northern
  • Nuclear Proteins
  • Nuclear Proteins: genetics
  • Nuclear Proteins: metabolism
  • Nucleic Acid
  • Nucleic Acid Conformation
  • Nude
  • Obesity
  • Obesity: metabolism
  • Oligonucleotide Array Sequence Analysis
  • Oligonucleotide Array Sequence Analysis: methods
  • Oligonucleotides
  • Oligonucleotides: metabolism
  • Oncogenes
  • Oncogenes: physiology
  • Oncogenic
  • Peyer's Patches
  • Peyer's Patches: immunology
  • Phenotype
  • Phenylacetates
  • Phosphoprotein Phosphatases
  • Phosphoprotein Phosphatases: genetics
  • Physiologic
  • Physiologic: genetics
  • Physiological
  • Plasmids
  • Poly I-C
  • Poly I-C: pharmacology
  • Post-Transcriptional
  • Prognosis
  • Promoter Regions
  • Protein Binding
  • Protein Biosynthesis
  • Protein-Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases: metabolism
  • Proteins
  • Proteins: genetics
  • Proteins: metabolism
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-2: genetics
  • Proto-Oncogene Proteins c-bcl-2: metabolism
  • Proto-Oncogene Proteins c-maf
  • Proto-Oncogene Proteins c-maf: genetics
  • Proto-Oncogene Proteins c-maf: physiology
  • Proto-Oncogene Proteins: genetics
  • Proto-Oncogene Proteins: metabolism
  • Proviruses
  • Proviruses: genetics
  • RNA
  • RNA Interference
  • RNA Precursors
  • RNA Precursors: genetics
  • RNA Precursors: metabolism
  • RNA Processing
  • RNA-Induced Silencing Complex
  • RNA-Induced Silencing Complex: metabolism
  • Rats
  • Receptor
  • Receptors
  • Recombinant Fusion Proteins
  • Recombinant Fusion Proteins: genetics
  • Recombinant Fusion Proteins: metabolism
  • Recombinant Proteins
  • Recombinant Proteins: metabolism
  • Recombination
  • Regression Analysis
  • Regulatory
  • Regulatory: cytology
  • Regulatory: enzymology
  • Regulatory: immunology
  • Regulatory: metabolism
  • Reporter
  • Retroviridae
  • Retroviridae Infections
  • Retroviridae Infections: genetics
  • Retroviridae Infections: virology
  • Retroviridae Proteins
  • Retroviridae: physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonuclease III
  • Ribonuclease III: metabolism
  • Ribonuclease III: physiology
  • Ribosomal Proteins
  • Ribosomal Proteins: genetics
  • Ribosomal Proteins: metabolism
  • SCID
  • Salmonella Infections
  • Sensitivity and Specificity
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology
  • Signal Transduction
  • Single-Stranded
  • Single-Stranded: metabolism
  • Small Interfering
  • Small Interfering: genetics
  • Small Interfering: metabolism
  • Somatic Hypermutation
  • Spleen
  • Spleen: immunology
  • Substrate Specificity
  • T-Cell
  • T-Cell: genetics
  • T-Cell: virology
  • T-Lymphocytes
  • T-Lymphocytes: cytology
  • T-Lymphocytes: immunology
  • T-Lymphocytes: metabolism
  • TATA-Box Binding Protein
  • TATA-Box Binding Protein: metabolism
  • Tetrahydrofolate Dehydrogenase
  • Tetrahydrofolate Dehydrogenase: genetics
  • Th1 Cells
  • Th1 Cells: cytology
  • Th1 Cells: immunology
  • Th2 Cells
  • Th2 Cells: cytology
  • Th2 Cells: immunology
  • Thrombopoiesis
  • Thrombopoiesis: genetics
  • Thymus Gland
  • Thymus Gland: cytology
  • Thymus Gland: immunology
  • Time Factors
  • Trans-Activators
  • Trans-Activators: genetics
  • Transcription
  • Transcription Factor TFIIB
  • Transcription Factor TFIIB: metabolism
  • Transcription Factors
  • Transcription Factors: metabolism
  • Transcriptional Activation
  • Transcriptional Activation: genetics
  • Transfection
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta: physiology
  • Transgenic
  • Transplantation
  • Tumor
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor-alpha: biosynthesis
  • Tumor Suppressor Proteins
  • Tumor Suppressor Proteins: metabolism
  • Tumor Virus Infections
  • Tumor Virus Infections: genetics
  • Tumor Virus Infections: virology
  • Untranslated
  • Untranslated: genetics
  • Untranslated: metabolism
  • Up-Regulation
  • Up-Regulation: drug effects
  • Vaccination
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor A: antagonists
  • Vascular Endothelial Growth Factor A: chemistry
  • Vascular Endothelial Growth Factor A: genetics
  • Vascular Endothelial Growth Factor A: metabolism
  • Vesicle-Associated Membrane Protein 3
  • Vesicle-Associated Membrane Protein 3: genetics
  • Viral
  • Viral: metabolism
  • Virus Integration
  • Virus Integration: physiology
  • Virus Latency
  • Virus Latency: drug effects
  • Western
  • Xenograft Model Antitumor Assays
  • Zebrafish
  • Zebrafish Proteins
  • Zebrafish Proteins: genetics
  • Zebrafish Proteins: metabolism
  • Zebrafish: anatomy & histology
  • Zebrafish: embryology
  • Zebrafish: metabolism
  • a1
  • apoptosis
  • at http
  • bak
  • bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2 Homologous Antagonist-Killer Protein: metabo
  • bcl-2-Associated X Protein
  • bcl-2-Associated X Protein: metabolism
  • bcl-X Protein
  • bcl-X Protein: metabolism
  • bcl-x
  • bcl-x l
  • bh3-only
  • genesdev
  • hematopoiesis
  • how the bcl-2 family
  • jak kinases
  • mcl-1
  • of proteins regulate programmed
  • org
  • received february 9
  • revised version accepted april
  • src kinases
  • supplemental material is available
  • www

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Authors

  • To-Ha Thai

  • Dinis Pedro Calado

  • Stefano Casola

  • K Mark Ansel

  • Changchun Xiao

  • Yingzi Xue

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