title: Vaccinia-related kinase 1 is required for the maintenance of undifferentiated spermatogonia in mouse male germ cells.
abstract: Vaccinia-related kinase 1 (VRK1) is a crucial protein kinase for mitotic regulation. VRK1 is known to play a role in germ cell development, and its deficiency results in sterility. Here we describe that VRK1 is essential for the maintenance of spermatogonial stem cells. To determine whether VRK1 plays a role in these cells, we assessed the population size of undifferentiated spermatogonia. Flow cytometry analyses showed that the number of undifferentiated spermatogonia was markedly reduced in VRK1-deficient testes. VRK1 was highly expressed in spermatogonial populations, and approximately 66% of undifferentiated spermatogonia that were sorted as an Ep-CAM+/c-kit-/alpha-6-integrin+ population showed a positive signal for VRK1. Undifferentiated stem cells expressing Plzf and Oct4 but not c-kit also expressed VRK1, suggesting that VRK1 is an intrinsic factor for the maintenance of spermatogonial stem cells. Microarray analyses of the global testicular transcriptome and quantitative RT-PCR of VRK1-deficient testes revealed significantly reduced expression levels of undifferentiated spermatogonial marker genes in early postnatal mice. Together, these results suggest that VRK1 is required for the proliferation and differentiation of undifferentiated spermatogonia, which are essential for spermatogenic cell maintenance.
authors.affiliation: Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Yoon Ha
authors.initials: YH
authors.lastname: Choi
authors.forename: Choon-Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Aram
authors.initials: A
authors.lastname: Kang
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
authors.forename: Sun-Kyoung
authors.initials: SK
authors.lastname: Im
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Jeong
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kong
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D000071858:Epithelial Cell Adhesion Molecule; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D039503:Integrin alpha6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013093:Spermatogonia / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology; D013737:Testis / Q000166:cytology
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D039503:Integrin alpha6; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C484518:Vrk1 protein, mouse