RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genetics

Background:

• Spermatogonial stem cells (SSCs) are crucial for maintaining male fertility.
• Understanding the regulatory mechanisms governing SSC development is essential for reproductive health.

Purpose of the Study:

• To elucidate the role of the homeobox protein RHOX10 in controlling SSC generation.
• To identify direct and indirect target genes regulated by RHOX10 in pro-spermatogonia (ProSG).

Main Methods:

• In vivo identification of RHOX10-regulated genes in ProSG.
• Direct RHOX10 target gene identification using iSLAMseq temporal induction assay.
• In vitro ProSG differentiation assay to study RHOX10 function.

Main Results:

• RHOX10 acts as a key transcription factor (TF) initiating a cascade controlling SSC generation.
• Identified temporal waves of RHOX10 direct and secondary target genes.
• Demonstrated RHOX10 promotes ProSG differentiation via a conserved cascade involving DMRT1 and ZBTB16.

Conclusions:

• RHOX10 is a critical regulator of mouse SSC generation and male fertility.
• The study provides a framework for defining transcription factor cascades in germ cell development.
• Findings offer insights into potential therapeutic targets for fertility disorders.