Document Detail


Effect of increased HoxB4 on human megakaryocytic development.
MedLine Citation:
PMID:  20599537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In order to produce clinically useful quantities of platelets ex vivo we may need to firstly enhance early self-renewal of hematopoietic stem cells (HSCs) and/or megakaryocyte (Mk) progenitors. The homeodomain transcription factor HoxB4 has been shown to be an important regulator of stem cell renewal and hematopoiesis; however, its effect on megakaryopoiesis is unclear. In this study, we investigated the effect of HoxB4 overexpression or RNA silencing on megakaryocytic development in the human TF1 progenitor cell line; we then used recombinant tPTD-HoxB4 fusion protein to study the effect of exogenous HoxB4 on megakaryocytic development of human CD34 positively-selected cord blood cells. We found that ectopic HoxB4 in TF1 cells increased the antigen expression of CD61and CD41a, increased the gene expression of thrombopoietin receptor (TpoR), Scl-1, Cyclin D1, Fog-1 and Fli-1 while it decreased c-Myb expression. HoxB4 RNA silencing in TF1 cells decreased the expression of CD61 and CD41a and decreased Fli-1 expression while it increased the expression of c-Myb. Recombinant tPTD-HoxB4 fusion protein increased the percentages and absolute numbers of CD41a and CD61 positive cells during megakaryocytic differentiation of CD34 positively-selected cord blood cells and increased the numbers of colony-forming unit-megakaryocyte (CFU-Mk). Adding tPTD-HoxB4 fusion protein increased the gene expression of TpoR, Cyclin D1, Fog-1 and Fli-1 while it inhibited c-Myb expression. Our data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord blood cells primarily by upregulating TpoR and Fli-1 expression and downregulating c-Myb expression. Increasing HoxB4 expression or adding recombinant HoxB4 protein might be a way to expand Mks for the production of platelets for use in transfusion medicine.
Authors:
Yiming Zhong; Brent Sullenbarger; Larry C Lasky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-22
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  398     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-08-03     Completed Date:  2010-09-08     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  377-82     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Culture Techniques
Cell Line
Cyclin D1 / genetics
Gene Expression Regulation*
Gene Silencing
Genetic Vectors
Homeodomain Proteins / genetics,  pharmacology,  physiology*
Humans
Integrin beta3 / metabolism
Lentivirus
Megakaryocyte Progenitor Cells / cytology*,  drug effects,  metabolism
Megakaryocytes / cytology*,  metabolism
Nuclear Proteins / genetics
Platelet Glycoprotein GPIb-IX Complex / metabolism
Platelet Transfusion
Proto-Oncogene Protein c-fli-1 / genetics
Proto-Oncogene Proteins c-myb / genetics
Recombinant Proteins / pharmacology
Thrombopoiesis / drug effects,  genetics*
Transcription Factors / genetics,  pharmacology,  physiology*
Grant Support
ID/Acronym/Agency:
R21 HL072088-01/HL/NHLBI NIH HHS; R21 HL072088-02/HL/NHLBI NIH HHS; R21 HL072088-03/HL/NHLBI NIH HHS; R21 HL072088-03S1/HL/NHLBI NIH HHS; R21HL072088/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/FLI1 protein, human; 0/HOXB4 protein, human; 0/Homeodomain Proteins; 0/ITGB3 protein, human; 0/Integrin beta3; 0/Nuclear Proteins; 0/Platelet Glycoprotein GPIb-IX Complex; 0/Proto-Oncogene Protein c-fli-1; 0/Proto-Oncogene Proteins c-myb; 0/Recombinant Proteins; 0/Transcription Factors; 0/ZFPM1 protein, human; 136601-57-5/Cyclin D1
Comments/Corrections

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