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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2011-3-22
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pubmed:abstractText |
MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21118986-10637270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21118986-10724173,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21118986-20589685,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/21118986-9393859
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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/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/CD150 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN125 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Mirn125 microRNA, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21505-10
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:21118986-Animals,
pubmed-meshheading:21118986-Antigens, CD,
pubmed-meshheading:21118986-Antigens, CD34,
pubmed-meshheading:21118986-Apoptosis,
pubmed-meshheading:21118986-Cell Differentiation,
pubmed-meshheading:21118986-Cell Lineage,
pubmed-meshheading:21118986-Cell Survival,
pubmed-meshheading:21118986-Gene Expression Profiling,
pubmed-meshheading:21118986-Hematopoietic Stem Cells,
pubmed-meshheading:21118986-Humans,
pubmed-meshheading:21118986-Lymphocyte Subsets,
pubmed-meshheading:21118986-Lymphocytes,
pubmed-meshheading:21118986-Mice,
pubmed-meshheading:21118986-Mice, Inbred C57BL,
pubmed-meshheading:21118986-MicroRNAs,
pubmed-meshheading:21118986-Microarray Analysis,
pubmed-meshheading:21118986-Receptors, Cell Surface,
pubmed-meshheading:21118986-Stem Cell Transplantation,
pubmed-meshheading:21118986-Transplantation Chimera
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pubmed:year |
2010
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pubmed:articleTitle |
MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.
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pubmed:affiliation |
Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
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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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