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CDK2 kinase activity is a regulator of male germ cell fate

Priti Singh1, Ravi K Patel2, Nathan Palmer3,4

  • 1Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY 14853, USA.

Development (Cambridge, England)
|October 5, 2019
PubMed

Insights

Precise regulation of cyclin-dependent kinase 2 (CDK2) activity is vital for male fertility. Deregulated CDK2 impairs the transition of gonocytes to spermatogonial stem cells (SSCs), leading to infertility.

Area of Science:

  • Reproductive Biology
  • Cell Cycle Regulation
  • Stem Cell Biology

Background:

  • Male fertility relies on establishing and maintaining a pool of spermatogonial stem cells (SSCs).
  • The balance between SSC renewal and differentiation is critical for long-term spermatogenesis.
  • Cell cycle regulation plays a key role in germ cell development.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase 2 (CDK2) in male germ cell development and spermatogonial stem cell differentiation.
  • To determine the impact of deregulated CDK2 activity on the gonocyte-to-spermatogonia transition.

Main Methods:

  • Generation and analysis of mice with a deregulated CDK2 allele (Cdk2).
  • Assessment of spermatogonial differentiation using lineage markers and proliferation analyses.
  • Single-cell RNA sequencing (scRNA-seq) to analyze germ cell development.
  • Biochemical and genetic assays to characterize CDK2 kinase activity.

Main Results:

  • Mice with the deregulated Cdk2 allele exhibit severe defects in spermatogonial differentiation.
  • Abnormal clusters of mitotically active SSC-like cells are observed, followed by apoptosis.
  • scRNA-seq data reveal delayed and defective differentiation of gonocytes into SSCs.
  • The Cdk2 allele acts as a gain-of-function mutation, increasing CDK2 kinase activity.

Conclusions:

  • Precise regulation of CDK2 kinase activity is essential for the gonocyte-to-spermatogonia transition.
  • Disruption of CDK2 regulation leads to impaired SSC differentiation and potential infertility.
  • CDK2 activity is crucial for maintaining spermatogenic homeostasis throughout life.
Keywords:
Cell cycleGonocytesMouseSpermatogonia

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