NOV (CCN3) functions as a regulator of human hematopoietic stem or progenitor cells.
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.
Gupta
Rajeev
R
Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, OX3 9DS, UK.
Hong
Dengli
D
Iborra
Francisco
F
Sarno
Samantha
S
Enver
Tariq
T
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D055513:Connective Tissue Growth Factor; D005822:Genetic Vectors; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055514:Nephroblastoma Overexpressed Protein; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526319:CCN3 protein, human; C526320:Ccn3 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor