Spermatogonial stem cells: updates from specification to clinical relevance

Area of Science:

• Reproductive Biology and Stem Cell Science
• Human Spermatogenesis and Germ Cell Development

Background:

• Human spermatogonia are crucial for understanding adult stem cell biology and hold therapeutic potential.
• Decades-old questions persist regarding the precise nature and classification of human spermatogonial stem cells.
• Advances in single-cell analysis offer unprecedented resolution into germ cell differentiation.

Purpose of the Study:

• To consolidate current knowledge on human spermatogonia, incorporating species comparisons of proliferative potential.
• To update the status of human spermatogonia for clinical applications.
• To review germ cell specification, epigenetic, and transcriptional features from primordial germ cells to adult spermatogonia.

Main Methods:

• Review of single-cell analysis studies providing high-resolution transcriptional profiles.
• Analysis of datasets on spermatogonial expansion models.
• Calculation of spermatogonial turnover and lifetime sperm production rates using the optical dissector approach.

Main Results:

• Single-cell RNA sequencing reveals transcriptional heterogeneity in germ cells before differentiation.
• Novel calculations suggest spermatogonia adapt to reproductive lifespan, balancing sperm output with genome integrity.
• Evidence supports debate on whether spermatogonia are a plastic population regulated by the stem cell niche.

Conclusions:

• Human spermatogonial biology, from embryonic to adult stages, is complex and requires further investigation.
• The concept of a 'true' stem cell versus a stem cell pool with diverse features needs re-evaluation.
• This review provides novel insights relevant to fertility, spermatogenesis, and fertility preservation research and clinical practice.