Plzf is required in adult male germ cells for stem cell self-renewal.
Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.
Buaas
F William
FW
Department of Genome Sciences, Box 357730, 1705 NE Pacific Street, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Kirsh
Andrew L
AL
Sharma
Manju
M
McLean
Derek J
DJ
Morris
Jamie L
JL
Griswold
Michael D
MD
de Rooij
Dirk G
DG
Braun
Robert E
RE
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050814:Octamer Transcription Factor-3; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C513267:Zbtb16 protein, mouse; D004247:DNA