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rdf:type |
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lifeskim:mentions |
umls-concept:C0009015,
umls-concept:C0017262,
umls-concept:C0018956,
umls-concept:C0024400,
umls-concept:C0031437,
umls-concept:C0185117,
umls-concept:C0205245,
umls-concept:C0443221,
umls-concept:C0680063,
umls-concept:C0936012,
umls-concept:C1332002,
umls-concept:C1515655,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2005-1-11
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pubmed:databankReference |
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pubmed:abstractText |
Hematopoietic cells can be highly enriched for repopulating ability based upon the efflux of the fluorescent Hoechst 33342 dye by sorting for SP (side population) cells, a phenotype attributed to expression of ABCG2, a member of the ABC transporter superfamily. Intriguingly, murine studies suggest that forced ABCG2 expression prevents hematopoietic differentiation. We cloned the full-length rhesus ABCG2 and introduced it into a retroviral vector. ABCG2-transduced human peripheral blood progenitor cells (PBPCs) acquired the SP phenotype but showed significantly reduced growth compared with control. Two rhesus macaques received autologous PBPCs split for transduction with the ABCG2 or control vectors. Marking levels were similar between fractions with no discrepancy between bone marrow and peripheral blood marking. Analysis for the SP phenotype among bone marrow and mature blood populations confirmed ABCG2 expression at levels predicted by vector copy number long term, demonstrating no block to differentiation in the large animal. In vitro studies showed selective protection against mitoxantrone among ABCG2-transduced rhesus PBPCs. Our results confirm the existence of rhesus ABCG2, establish its importance in conferring the SP phenotype, suggest no detrimental effect of its overexpression upon differentiation in vivo, and imply a potential role for its overexpression as an in vivo selection strategy for gene therapy applications.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/CYBB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte Colony-Stimulating...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitoxantrone,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BrennerSebastianS,
pubmed-author:DonahueRobert ERE,
pubmed-author:KangElizabeth MEM,
pubmed-author:KirbyMarthaM,
pubmed-author:KrouseAllen EAE,
pubmed-author:LangemeijerSaskia MSM,
pubmed-author:MalechHarry LHL,
pubmed-author:PerlShiraS,
pubmed-author:PhangOswald AOA,
pubmed-author:TisdaleJohn FJF,
pubmed-author:UedaTakahiroT
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
991-8
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:15516692-ATP-Binding Cassette Transporters,
pubmed-meshheading:15516692-Animals,
pubmed-meshheading:15516692-Antigens, CD34,
pubmed-meshheading:15516692-Cell Lineage,
pubmed-meshheading:15516692-Cell Proliferation,
pubmed-meshheading:15516692-Cells, Cultured,
pubmed-meshheading:15516692-Cloning, Molecular,
pubmed-meshheading:15516692-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:15516692-Humans,
pubmed-meshheading:15516692-Macaca mulatta,
pubmed-meshheading:15516692-Membrane Glycoproteins,
pubmed-meshheading:15516692-Mitoxantrone,
pubmed-meshheading:15516692-Molecular Sequence Data,
pubmed-meshheading:15516692-NADPH Oxidase,
pubmed-meshheading:15516692-Neoplasm Proteins,
pubmed-meshheading:15516692-Phenotype,
pubmed-meshheading:15516692-Stem Cell Factor,
pubmed-meshheading:15516692-Time Factors,
pubmed-meshheading:15516692-Transduction, Genetic
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pubmed:year |
2005
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pubmed:articleTitle |
Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo.
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pubmed:affiliation |
Molecular and Clinical Hematology Branch, NIDDK, National Instiutes of Health, Bethesda, Maryland 20892, USA.
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pubmed:publicationType |
Journal Article
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