title: SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis.
abstract: SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1(-/-) animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at >20 weeks of age) was preceded by a transient increase in the number of undifferentiated A(aligned) (A(al)) spermatogonia in younger mice (at >10 weeks of age). The number of primary Spoc1(-/-) gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1(-/-) testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.
authors.affiliation: University Hospital Erlangen, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Bördlein
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.forename: Claudia
authors.initials: C
authors.lastname: Nelkenbrecher
authors.forename: Tina
authors.initials: T
authors.lastname: Molter
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.forename: Christine
authors.initials: C
authors.lastname: Dippold
authors.forename: Kerstin
authors.initials: K
authors.lastname: Birke
authors.forename: Sarah
authors.initials: S
authors.lastname: Kinkley
authors.forename: Hannah
authors.initials: H
authors.lastname: Staege
authors.forename: Hans
authors.initials: H
authors.lastname: Will
authors.forename: Andreas
authors.initials: A
authors.lastname: Winterpacht
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C503048:PHF13 protein, human; D014157:Transcription Factors