Single-Cell RNA Sequencing Analysis Reveals Sequential Cell Fate Transition during Human Spermatogenesis

Area of Science:

• Reproductive Biology
• Genetics
• Developmental Biology

Background:

• Spermatogenesis is crucial for male fertility and genetic transmission.
• The detailed developmental pathways of human spermatogenesis are not fully understood.

Purpose of the Study:

• To reconstruct the transcriptional landscape of human spermatogenesis.
• To identify stage-specific genes and cellular subtypes.
• To investigate gene expression alterations in nonobstructive azoospermia (NOA).

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of 2,854 testicular cells from normal donors.
• scRNA-seq analysis of 174 testicular cells from one NOA patient.
• Hierarchical modeling to define developmental progression.

Main Results:

• Established a developmental model with distinct subtypes of spermatogonia, spermatocytes, and spermatids.
• Identified novel stage-specific marker genes including HMGA1, PIWIL4, TEX29, SCML1, and CCDC112.
• Detected altered gene expression in testicular somatic cells of an NOA patient.

Conclusions:

• Provides a comprehensive map of human spermatogenesis at the single-cell level.
• Offers insights into the molecular mechanisms of male germ cell development.
• Facilitates the diagnosis and understanding of male infertility and reproductive disorders.