March 14, 2025
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A pair of new studies published in Nature Structural & Molecular Biology by researchers from UC Davis and collaborators at the University of Utah School of Medicine, leveraged Arima Genomics’ Hi-C technology as part of an effort to understand how sperm develop. The research, which was funded in part by the National Institutes of Health and Japanese Society for Promotion of Science, identified two proteins associated with sperm cell development – SCML2, which facilitates the DNA unfolding that enables sperm cell development and CTCF, which helps activate differentiation process that generates haploid sperm.
Identifying these proteins required developing a new understanding of the genomics of sperm development to uncover the molecular mechanisms that regulate male fertility and may contribute to infertility. Further research in this area could offer new insights into potential therapeutic interventions to address male infertility.
The importance of better understanding the genomics of sperm development
This research centered on the role of spermatogonial stem cells (SSCs). These special cells responsible for sperm production must balance their own renewal with their differentiation into sperm. A disturbance to this balance could result in inadequate sperm development and male infertility.
The researchers identified several proteins which help regulate the process of preparing SSC DNA for sperm development, ensuring that cells divide properly to enable sperm formation. Specifically, SCML2, helps the SSC switch between initiating mitosis (a normal cell division process) and meiosis (the type of cell division that creates sperm). Similarly, CTCF, a chromatin regulator, helps organize the DNA into the 3D shape that facilitates the expression of genes critical to sperm development.
How Hi-C facilitated these discoveries
Arima Genomics’ Hi-C technology contributed to this research by enabling high-resolution chromatin conformation capture experiments. These experiments provided detailed maps of the 3D organization of chromatin in SSCs and in sperm, allowing researchers to observe how different proteins facilitated transcription and gene expression processes regulating SSC behavior and sperm development.
