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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-3-31
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pubmed:abstractText |
Hematopoietic stem cells (HSCs) are enriched for aldehyde dehydrogenase (ALDH) activity and ALDH is a selectable marker for human HSCs. However, the function of ALDH in HSC biology is not well understood. We sought to determine the function of ALDH in regulating HSC fate. Pharmacologic inhibition of ALDH with diethylaminobenzaldehyde (DEAB) impeded the differentiation of murine CD34(-)c-kit(+)Sca-1(+)lineage(-) (34(-)KSL) HSCs in culture and facilitated a ninefold expansion of cells capable of radioprotecting lethally irradiated mice compared to input 34(-)KSL cells. Treatment of bone marrow (BM) 34(-)KSL cells with DEAB caused a fourfold increase in 4-week competitive repopulating units, verifying the amplification of short-term HSCs (ST-HSCs) in response to ALDH inhibition. Targeted siRNA of ALDH1a1 in BM HSCs caused a comparable expansion of radioprotective progenitor cells in culture compared to DEAB treatment, confirming that ALDH1a1 was the target of DEAB inhibition. The addition of all trans retinoic acid blocked DEAB-mediated expansion of ST-HSCs in culture, suggesting that ALDH1a1 regulates HSC differentiation via augmentation of retinoid signaling. Pharmacologic inhibition of ALDH has therapeutic potential as a means to amplify ST-HSCs for transplantation purposes.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1549-4918
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pubmed:author |
pubmed-author:ChaoNelson JNJ,
pubmed-author:ChuteJohn PJP,
pubmed-author:DaherPamelaP,
pubmed-author:DoanPhuongP,
pubmed-author:HimburgHeather AHA,
pubmed-author:McDonnellDonald PDP,
pubmed-author:MeadowsSarah KSK,
pubmed-author:MuramotoGarrett GGG,
pubmed-author:RussellJ LaurenJL,
pubmed-author:SafiRachidR,
pubmed-author:SalterAlice BAB,
pubmed-author:StormsRobert WRW
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pubmed:issnType |
Electronic
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pubmed:day |
31
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
523-34
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pubmed:meshHeading |
pubmed-meshheading:20054864-Aldehyde Dehydrogenase,
pubmed-meshheading:20054864-Animals,
pubmed-meshheading:20054864-Antineoplastic Agents,
pubmed-meshheading:20054864-Cell Differentiation,
pubmed-meshheading:20054864-Cell Division,
pubmed-meshheading:20054864-Cell Proliferation,
pubmed-meshheading:20054864-Cells, Cultured,
pubmed-meshheading:20054864-Cytoprotection,
pubmed-meshheading:20054864-Enzyme Inhibitors,
pubmed-meshheading:20054864-Hematopoietic Stem Cells,
pubmed-meshheading:20054864-Humans,
pubmed-meshheading:20054864-Mice,
pubmed-meshheading:20054864-Mice, Congenic,
pubmed-meshheading:20054864-Mice, Inbred C57BL,
pubmed-meshheading:20054864-RNA, Small Interfering,
pubmed-meshheading:20054864-Radiation, Ionizing,
pubmed-meshheading:20054864-Signal Transduction,
pubmed-meshheading:20054864-Stem Cell Transplantation,
pubmed-meshheading:20054864-Tretinoin,
pubmed-meshheading:20054864-p-Aminoazobenzene
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pubmed:year |
2010
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pubmed:articleTitle |
Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with radioprotective capacity.
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pubmed:affiliation |
Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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