Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation

Area of Science:

• Reproductive Biology
• Epigenetics
• Chromatin Structure

Background:

• Spermatogonial stem cells (SSCs) self-renew and differentiate, a key process for male fertility.
• Differentiation commits cells to meiosis, involving irreversible changes.
• The 3D chromatin architecture differences between SSCs and differentiating spermatogonia (Di-SG) remain largely unexplored.

Purpose of the Study:

• To investigate the 3D chromatin structure and dynamics during spermatogonial differentiation.
• To compare chromatin organization between undifferentiated spermatogonia (including SSCs) and Di-SG.
• To elucidate the relationship between chromatin architecture and gene expression during this process.

Main Methods:

• In situ high-throughput chromosome conformation capture (Hi-C).
• RNA sequencing (RNA-seq).
• Chromatin immunoprecipitation sequencing (ChIP-seq) on porcine cells.

Main Results:

• Differentiating spermatogonia (Di-SG) exhibit less compact chromatin, weakened compartmentalization, and reduced topologically associating domains compared to undifferentiated cells.
• A/B compartments and topologically associating domains correlate with dynamic gene expression during differentiation.
• Promoter-enhancer interactions contribute to premeiotic transcriptional regulation.

Conclusions:

• Diminished higher-order chromatin architecture in Di-SG may be preprogrammed.
• The study reveals the interplay between 3D chromatin structure and gene expression in spermatogonial differentiation.
• Findings offer insights into SSC self-renewal, differentiation, and male infertility.