title: Characterization of human spermatogonial stem cell markers in fetal, pediatric, and adult testicular tissues.
abstract: Autologous spermatogonial stem cell (SSC) transplantation is a potential therapeutic modality for patients with azoospermia following cancer treatment. For this promise to be realized, definitive membrane markers of prepubertal and adult human SSCs must be characterized in order to permit SSC isolation and subsequent expansion. This study further characterizes the markers of male gonocytes, prespermatogonia, and SSCs in humans. Human fetal, prepubertal, and adult testicular tissues were analyzed by confocal microscopy, fluorescence-activated cell sorting, and qRT-PCR for the expression of unique germ cell membrane markers. During male fetal development, THY1 and KIT (C-Kit) are transient markers of gonocytes but not in prespermatogonia and post-natal SSCs. Although KIT expression is detected in gonocytes, THY1 expression is also detected in the somatic component of the fetal testes in addition to gonocytes. In the third trimester of gestation, THY1 expression shifts exclusively to the somatic cells of the testes where it continues to be detected only in the somatic cells postnatally. In contrast, SSEA4 expression was only detected in the gonocytes, prespermatogonia, SSCs, and Sertoli cells of the fetal and prepubertal testes. After puberty, SSEA4 expression can only be detected in primitive spermatogonia. Thus, although THY1 and KIT are transient markers of gonocytes, SSEA4 is the only common membrane marker of gonocytes, prespermatogonia, and SSCs from fetal through adult human development. This finding is essential for the isolation of prepubertal and adult SSCs, which may someday permit fertility preservation and reversal of azoospermia following cancer treatment.
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Altman
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Yango
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA.
authors.forename: Radwa
authors.initials: R
authors.lastname: Moustafa
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Smith
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Klatsky
authors.affiliation: Department of ObstetricsGynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USAHelen Schneider Hospital for WomenRabin Medical Center, Petah Tikva, IsraelDepartment of UrologyUniversity of California, San Francisco, San Francisco, California, USADepartment of Obstetrics and GynecologyAlbert Einstein University, Bronx, New York, USA trann@obgyn.ucsf.edu.
authors.forename: Nam D
authors.initials: ND
authors.lastname: Tran
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D000367:Age Factors; D015415:Biomarkers / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism*; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D055746:Stage-Specific Embryonic Antigens; D018800:Thy-1 Antigens; C066584:stage-specific embryonic antigen-4; D019009:Proto-Oncogene Proteins c-kit