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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD34 / analysis
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Cell Line
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Cells, Cultured
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Colony-Forming Units Assay
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Connective Tissue Growth Factor
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Genetic Vectors
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Hematopoiesis
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Hematopoietic Stem Cell Transplantation
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / physiology*
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Humans
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / physiology*
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / physiology*
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Lentivirus / genetics
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Nephroblastoma Overexpressed Protein
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RNA Interference
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Recombinant Proteins / metabolism
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Transfection
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Transplantation, Heterologous
Substances
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Antigens, CD34
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CCN2 protein, human
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CCN2 protein, mouse
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CCN3 protein, human
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Ccn3 protein, mouse
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Immediate-Early Proteins
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Intercellular Signaling Peptides and Proteins
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Nephroblastoma Overexpressed Protein
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Recombinant Proteins
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Connective Tissue Growth Factor