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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-1-6
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pubmed:abstractText |
The in vivo regulation of hematopoietic stem cell (HSC) function is poorly understood. Here, we show that hematopoietic repopulation can be augmented by administration of a glycogen synthase kinase-3 (GSK-3) inhibitor to recipient mice transplanted with mouse or human HSCs. GSK-3 inhibitor treatment improved neutrophil and megakaryocyte recovery, recipient survival and resulted in enhanced sustained long-term repopulation. The output of primitive Lin(-)c-Kit(+)Sca-1(+) cells and progenitors from HSCs increased upon GSK-3 inhibitor treatment without altering secondary repopulating ability, suggesting that the HSC pool is maintained while overall hematopoietic reconstitution is increased. GSK-3 inhibitors were found to modulate gene targets of Wnt, Hedgehog and Notch pathways in cells comprising the primitive hematopoietic compartment without affecting mature cells. Our study establishes GSK-3 as a specific in vivo modulator of HSC activity, and suggests that administration of GSK-3 inhibitors may provide a clinical means to directly enhance the repopulating capacity of transplanted HSCs.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hedgehog Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
89-98
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16341242-Animals,
pubmed-meshheading:16341242-Blood Glucose,
pubmed-meshheading:16341242-Cell Proliferation,
pubmed-meshheading:16341242-Cell Transplantation,
pubmed-meshheading:16341242-Cells, Cultured,
pubmed-meshheading:16341242-Culture Media, Serum-Free,
pubmed-meshheading:16341242-Enzyme Inhibitors,
pubmed-meshheading:16341242-Fetal Blood,
pubmed-meshheading:16341242-Flow Cytometry,
pubmed-meshheading:16341242-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16341242-Glycogen Synthase Kinase 3,
pubmed-meshheading:16341242-Green Fluorescent Proteins,
pubmed-meshheading:16341242-Hedgehog Proteins,
pubmed-meshheading:16341242-Hematopoietic Stem Cells,
pubmed-meshheading:16341242-Humans,
pubmed-meshheading:16341242-Leukocytes, Mononuclear,
pubmed-meshheading:16341242-Megakaryocytes,
pubmed-meshheading:16341242-Mice,
pubmed-meshheading:16341242-Mice, Inbred C57BL,
pubmed-meshheading:16341242-Mice, SCID,
pubmed-meshheading:16341242-Mice, Transgenic,
pubmed-meshheading:16341242-Models, Biological,
pubmed-meshheading:16341242-Neutrophils,
pubmed-meshheading:16341242-Receptors, Notch,
pubmed-meshheading:16341242-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16341242-Stem Cell Transplantation,
pubmed-meshheading:16341242-Stem Cells,
pubmed-meshheading:16341242-Time Factors,
pubmed-meshheading:16341242-Trans-Activators,
pubmed-meshheading:16341242-Wnt Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation.
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pubmed:affiliation |
Krembil Centre for Stem Cell Biology, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada, N6A 5K8.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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