A distinct expression pattern of cyclin K in mammalian testes suggests a functional role in spermatogenesis.

Xiaocong Xiang,Chunlei Yang,Guangxin Luan,Zhi-Xiong Xiao,Tingjun Lei,Qintong Li,Jingli Zhang,Li Deng,Xudong Zhang,Qian Li,Stefan Schlatt

doi:10.1371/journal.pone.0101539

Xiaocong Xiang, Chunlei Yang + Show 9 more

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https://doi.org/10.1371/journal.pone.0101539

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Abstract

Germ cell and embryonic stem cells are inextricably linked in many aspects. Remarkably both can generate all somatic cell types in organisms. Yet the molecular regulation accounting for these similarities is not fully understood. Cyclin K was previously thought to associate with CDK9 to regulate gene expression. However, we and others have recently shown that its cognate interacting partners are CDK12 and CDK13 in mammalian cells. We further demonstrated that cyclin K is essential for embryonic stem cell maintenance. In this study, we examined the expression of cyclin K in various murine and human tissues. We found that cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. During neonatal spermatogenesis, cyclin K is highly expressed in gonocytes and spermatogonial stem cells. In adult testes, cyclin K can be detected in spermatogonial stem cells but is absent in differentiating spermatogonia, spermatids and spermatozoa. Interestingly, the strongest expression of cyclin K is detected in primary spermatocytes. In addition, we found that cyclin K is highly expressed in human testicular cancers. Knockdown of cyclin K in a testicular cancer cell line markedly reduces cell proliferation. Collectively, we suggest that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance.

Highlights

It has long been recognized that embryonic stem cells (ESCs) and germ cells share important similarities
It was previously thought that it interacts with CDK9 to regulate transcription elongation, recent findings from several labs have established that cyclin K (CycK) interacts with CDK12 and CDK13 but not CDK9 [17,20,21]
CycK, CDK12 and CDK13 are localized in nuclear speckles, indicating that they may be involved in some aspects of transcription [24,30]

Summary

Introduction

It has long been recognized that embryonic stem cells (ESCs) and germ cells share important similarities Both are pluripotent, that is, they can generate all somatic cell types in organisms. That is, they can generate all somatic cell types in organisms Underlying this remarkable ability is inextricably linked molecular regulatory networks that when dysregulated can lead to human diseases such as cancer [1]. Spermatogenesis is the process by which sperm cells or spermatozoa are produced from PGCs in the seminiferous tubules of the testes [6,7,8]. Leydig cells and myoid cells in interstitial tissues may contribute to spermatogenesis microenvironment [8]

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