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.
Highlights
Spermatogenesis is a highly productive and tightly regulated process
As previous study revealed that this mouse is hypomorphic for Vaccinia-related kinase 1 (VRK1), we confirmed some of full length VRK1 was expressed in the homozygote (Figure S1) [17]
This study investigated the functional importance of VRK1 for the maintenance of mammalian spermatogonial stem cells
Summary
Multiple cell types, including somatic and germ cells, play different roles to maintain continuous sperm cell production. To sustain the germ cell population, the active proliferation of spermatogonia is required. Spermatogonial stem cells (SSCs) are adult stem cells in the testes that support the germ cell pool throughout a male’s life. SSCs can self-renew and differentiate into spermatozoa. These stem cells can proliferate rapidly to restore the germ cell population if that population becomes diminished (e.g., following exposure to a toxic chemical agent or irradiation). Unidentified subpopulations of undifferentiated spermatogonia have stem cell capabilities. Undifferentiated spermatogonia comprise Asingle (As), Apaired (Apr), and Aaligned (Aal) cells among type A spermatogonia [2,3,4]
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