Essential role of Plzf in maintenance of spermatogonial stem cells.
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/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.
Costoya
José A
JA
Cancer Biology and Genetics Program, Department of Pathology Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Hobbs
Robin M
RM
Barna
Maria
M
Cattoretti
Giorgio
G
Manova
Katia
K
Sukhwani
Meena
M
Orwig
Kyle E
KE
Wolgemuth
Debra J
DJ
Pandolfi
Pier Paolo
PP
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D015870:Gene Expression; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C513267:Zbtb16 protein, mouse