Plzf is required in adult male germ cells for stem cell self-renewal

• Published in: Nature genetics Vol. 36; no. 6; pp. 647 - 652
• Main Authors: Buaas, F William, Morris, Jamie L, Griswold, Michael D, Kirsh, Andrew L, McLean, Derek J, Braun, Robert E, Sharma, Manju, de Rooij, Dirk G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-06-2004
• Subjects: Animals; Base Sequence; Biological and medical sciences; Biology; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Codon, Nonsense; DNA - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epigenesis, Genetic; Fundamental and applied biological sciences. Psychology; Gene expression; Gene mutations; Genetic aspects; Genotype & phenotype; Germ cells; Kruppel-Like Transcription Factors; Male; Males; Mammals; Medical research; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Molecular and cellular biology; Mutants; Mutation; Octamer Transcription Factor-3; Physiological aspects; Promyelocytic Leukemia Zinc Finger Protein; Sperm; Spermatogenesis; Spermatogonia - cytology; Spermatogonia - metabolism; Spermatogonia - transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Testes; Testis - cytology; Transcription Factors - genetics; Transcription Factors - metabolism; United States; United States > US; Human; Vertebrata; Mammalia; Mouse; Spermatogenesis; Stem cell; Rodentia; Adult; Male; Germinal cell; Transcription factor
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1366

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.