Essential role of Plzf in maintenance of spermatogonial stem cells

被引:770
作者
Costoya, JA
Hobbs, RM
Barna, M
Cattoretti, G
Manova, K
Sukhwani, M
Orwig, KE
Wolgemuth, DJ
Pandolfi, PP
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Pathol, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA
[2] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Pathol, Dev Biol Program, Mol Cytol Core Facil, New York, NY 10021 USA
[4] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA
[5] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
[6] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/ng1367
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ cells of the testis, self-renew and differentiate into sperm(1,2). Here we show that Zfp145, encoding the transcriptional repressor Plzf, has a crucial role in spermatogenesis. Zfp145 expression was restricted to gonocytes and undifferentiated spermatogonia and was absent in tubules of W/W-v mutants that lack these cells. Mice lacking Zfp145 underwent a progressive loss of spermatogonia with age, associated with increases in apoptosis and subsequent loss of tubule structure but without overt differentiation defects or loss of the supporting Sertoli cells. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in the adult. Microarray analysis of isolated spermatogonia from Zfp145-null mice before testis degeneration showed alterations in the expression profile of genes associated with spermatogenesis. These results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool.
引用
收藏
页码:653 / 659
页数:7
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