(371) Identification of the Interleukin-7 System in Testicular Cells: Potential Role in Spermatogenesis Development

Xin Zhang¹; Qiqi Cao¹;Qianlan Xu¹; Huong Huynh¹; Haiqi Chen¹
1. Cecil H. and Ida Green Center for Reproductive Biology Sciences, UT Southwestern Medical Center Dallas, Texas, USA

Abstract Text:

The mammalian spermatogenesis is supported by a population of spermatogonial stem cells (SSCs), which are a group of adult stem cells with the potential of self-renewal and differentiation in the testis. The self-renewal of SSCs results in the maintenance of a stem cell pool, while the differentiation and proliferation of SSCs lead to the formation of sperm. The dynamic balance between SSC self-renewal and differentiation is co-regulated by intrinsic gene programs and extrinsic stimuli from the SSC microenvironment called the ‘niche’. Communications between the SSCs and the niche are largely mediated by ligands from the surrounding somatic cells and receptors expressed by SSCs. Upon ligand binding to SSC receptors, the downstream signaling pathways and gene programs are activated to regulate the SSC fate. To date, while many ligand-receptor pairs between somatic cells and SSCs have been discovered, the molecular mechanism of regulating SSC functions is still not well understood. Therefore, we try to develop a new CRISPR screen approach that systematically deciphers the interactions in the SSC stem niche by directly screening for ligand and receptor pairs in vivo. The novel method is first proposed for conducting the CRISPR screen in testes in vivo by combining single-cell RNA sequencing and spatial transcriptomics. Compared to the traditional knockout mouse models, the method is scalable and cost-effective. Meanwhile, the application of the method will provide a better understanding of the process regulating SSC functions which is key to the field of stem cell biology, and ultimately improve targeted therapies for male infertility.