Source:http://linkedlifedata.com/resource/pubmed/id/20308578
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rdf:type | |
lifeskim:mentions |
umls-concept:C0040732,
umls-concept:C0249197,
umls-concept:C0288472,
umls-concept:C0598086,
umls-concept:C0598388,
umls-concept:C0679932,
umls-concept:C0919418,
umls-concept:C1415887,
umls-concept:C1419040,
umls-concept:C1420433,
umls-concept:C1420626,
umls-concept:C1424666,
umls-concept:C1517945,
umls-concept:C1521797,
umls-concept:C2919017
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pubmed:issue |
14
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pubmed:dateCreated |
2010-4-7
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pubmed:abstractText |
Spermatogonial stem cells (SSCs) undergo self-renewal division to support spermatogenesis. Although several positive regulators of SSC self-renewal have been identified, little is known about the mechanisms that negatively regulate SSCs. Here we developed a novel transplantation assay for SSCs and demonstrate that p21 and p27 cyclin-dependent kinase inhibitors play critical roles in SSC self-renewal and differentiation. Overexpression of p21 or p27 abrogated proliferation of cultured SSCs in vitro, and their expression levels were downregulated by exogenous self-renewal signals. In contrast, no apparent defects were found in p21 or p27-deficient SSCs by spermatogonial transplantation. However, competitive spermatogonial transplantation with WT SSCs revealed that the loss of either gene causes distortion of germline transmission: p21-deficiency facilitated mutant offspring production, whereas germline transmission was limited by p27-deficiency. Serial transplantation also showed that the loss of p27, but not p21, decreases secondary colony formation, suggesting that appropriate amounts of p27 are necessary for sustaining SSC self-renewal. Thus, p21 and p27 cyclin-dependent kinase inhibitors play critical roles in germline transmission by regulating the balance between SSC self-renewal and differentiation, and competitive spermatogonial transplantation technique will be useful for analyzing subtle defects in spermatogenesis that are not evident by traditional spermatogonial transplantation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1091-6490
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
6
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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 |
6210-5
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pubmed:dateRevised |
2010-10-7
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pubmed:meshHeading |
pubmed-meshheading:20308578-Animals,
pubmed-meshheading:20308578-Cell Differentiation,
pubmed-meshheading:20308578-Cell Proliferation,
pubmed-meshheading:20308578-Cells, Cultured,
pubmed-meshheading:20308578-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:20308578-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:20308578-Male,
pubmed-meshheading:20308578-Mice,
pubmed-meshheading:20308578-Spermatogonia,
pubmed-meshheading:20308578-Stem Cell Transplantation,
pubmed-meshheading:20308578-Stem Cells
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pubmed:year |
2010
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pubmed:articleTitle |
Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation.
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pubmed:affiliation |
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. mshinoha@virus.kyoto-u.ac.jp
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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