Essential role of Plzf in maintenance of spermatogonial stem cells

José A. Costoya, Robin M. Hobbs, Maria Barna, Giorgio Cattoretti, Katia Manova, Meena Sukhwani, Kyle E. Orwig, Debra J. Wolgemuth, Pier Paolo Pandolfi

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685 Citations (Scopus)

Abstract

Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ cells of the testis, self-renew and differentiate into sperm. 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/Wv 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.

Original languageEnglish
Pages (from-to)653-659
Number of pages7
JournalNature Genetics
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

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