RRC ID |
11774
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著者 |
Noda S, Ichikawa H, Miyoshi H.
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タイトル |
Hematopoietic stem cell aging is associated with functional decline and delayed cell cycle progression.
|
ジャーナル |
Biochem Biophys Res Commun
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Abstract |
The molecular mechanisms underlying hematopoietic stem cell (HSC) aging remain to be elucidated. In this study, we investigated age-related changes in the functional and phenotypic properties of murine HSCs. Consistent with previous studies, we found that the number and frequency of CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cells, a highly enriched HSC population, significantly increased in old mice, though their repopulating ability was reduced. Continuous bromodeoxyuridine labeling revealed a significant delay in the cell cycle progression of CD34(-)KSL cells in old mice. This delay was also observed in young recipients transplanted with whole bone marrow cells from old mice. When cultured in vitro, CD34(-)KSL cells from old mice showed a greater capacity to give rise to primitive CD48(-)KSL cells with reduced HSC activity. Gene expression profiling identified age-related changes in the expression of several cell cycle regulatory genes, including p21/Cdkn1a and p18/Cdkn2c. These results support the notion that HSC aging is largely regulated by an intrinsic genetic program.
|
巻・号 |
383(2)
|
ページ |
210-5
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公開日 |
2009-5-29
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DOI |
10.1016/j.bbrc.2009.03.153
|
PII |
S0006-291X(09)00655-X
|
PMID |
19345668
|
MeSH |
Animals
Cell Cycle* / genetics
Cell Proliferation
Cells, Cultured
Cellular Senescence* / genetics
Gene Expression
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism
Hematopoietic Stem Cells / physiology*
Mice
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
|
IF |
2.985
|
引用数 |
26
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
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リソース情報 |
実験動物マウス |
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