title: Transcription Factor GLIS3: A New and Critical Regulator of Postnatal Stages of Mouse Spermatogenesis.
abstract: In this study, we identify a novel and essential role for the Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in the regulation of postnatal spermatogenesis. We show that GLIS3 is expressed in gonocytes, spermatogonial stem cells (SSCs) and spermatogonial progenitors (SPCs), but not in differentiated spermatogonia and later stages of spermatogenesis or in somatic cells. Spermatogenesis is greatly impaired in GLIS3 knockout mice. Loss of GLIS3 function causes a moderate reduction in the number of gonocytes, but greatly affects the generation of SSCs/SPCs, and as a consequence the development of spermatocytes. Gene expression profiling demonstrated that the expression of genes associated with undifferentiated spermatogonia was dramatically decreased in GLIS3-deficient mice and that the cytoplasmic-to-nuclear translocation of FOXO1, which marks the gonocyte-to-SSC transition and is necessary for SSC self-renewal, is inhibited. These observations suggest that GLIS3 promotes the gonocyte-to-SSC transition and is a critical regulator of the dynamics of early postnatal spermatogenesis. Stem Cells 2016;34:2772-2783.
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Hong Soon
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Lichti-Kaiser
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Liao
authors.affiliation: Molecular Genomics Core, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gerrish
authors.affiliation: Division of Intramural Research, Flow Cytometry Center, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Bortner
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Humphrey H-C
authors.initials: HH
authors.lastname: Yao
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Eddy
authors.affiliation: Immunity, Inflammation and Disease Laboratory, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Anton M
authors.initials: AM
authors.lastname: Jetten
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; C478000:Glis3 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators
keywords: GLIS3; Gene expression; Spermatogenesis; Spermatogonial stem cell