Single-cell RNA sequencing reveals the spatio-temporal expression profile of SARS-CoV-2 related receptor in human and mouse testes

ABSTRACT

Objective: To analyze the spatio-temporal expression profile of angiotensin-converting enzyme 2 (ACE2), the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in human and mouse testes based on single-cell RNA sequencing (scRNA-Seq). Methods: Ten testicular tissues from humans and nine testicular tissues from C57BL/6 mice with normal developmental stages were collected and digested into single cell suspensions by enzyme, and then the cell-gene expression matrixes were obtained by scRNA-Seq standard processing procedures. After quality control, data standardization, batch effect processing, clustering, and dimensionality reduction, each subgroup of cells was annotated based on known testicular cell bio-markers to clarify the expression patterns and differences of ACE2 in human and mouse testes with normal developmental stages. Results: In this study, nine testicular cell subgroups found in human and mice were identified, including three subgroups of germ cells (spermatogonia, spermatocytes, and spermatids/sperm) and six subgroups of somatic cells (Sertoli cells, macrophages, vascular smooth muscle cells, endothelial cells, Leydig cells, and peritubular myoid cells). In terms of spatial distribution, ACE2 was predominantly expressed in human Sertoli cells in adult testes, and also expressed in Leydig cells, peritubular myoid cells, and germ cells. In terms of time scale, the transcription abundance of ACE2 in human Sertoli cells increased with the development of testis, and the expression level of ACE2 in Sertoli cells after puberty was significantly higher than that in infancy and childhood (P=0.000). Judging from the stages of mouse testicular development, the expression patterns of Ace2 were both significantly different from those in humans. In testis of the 5-week-old adult C57BL/6 mouse, the transcription level of Ace2 was low and it was mainly expressed in vascular smooth muscle cells (P=0.000), while the number of Ace2 positive cell in Sertoli cells was extremely low. Conclusion: SARS-CoV-2 may mainly infects human testis through Sertoli cells, and the conventional C57BL/6 mouse model is not suitable to simulate the effect of SARS-CoV-2 infection on human testicular function.