Single-cell RNAseq analysis of testicular germ and somatic cell development during the perinatal period

Abstract

Pro-spermatogonia (SG) serve as the gateway to spermatogenesis. Using single-cell RNA sequencing (RNAseq), we studied the development of ProSG, their SG descendants, and testicular somatic cells, during the perinatal period in mice. We identified both gene and protein markers for 3 temporally distinct ProSG cell subsets, including a migratory cell population with a distinct transcriptome from the previously defined T1- and T2-ProSG stages. This intermediate (I)-ProSG subset translocates from the center of seminiferous tubules to the spermatogonial stem cell (SSC) “niche” in its periphery soon after birth. We identified 3 undifferentiated SG subsets at postnatal day 7, each of which express distinct genes, including transcription factor and signaling genes. Two of these subsets have the characteristics of newly emergent SSCs. We also molecularly defined the development of Sertoli, Leydig, and peritubular myoid cells during the perinatal period, allowing us to identify candidate signaling pathways acting between somatic and germ cells in a stage-specific manner during the perinatal period. Our study provides a rich resource for those investigating testicular germ and somatic cell developmental during the perinatal period.

Transcriptome profiling reveals signaling conditions dictating human spermatogonia fate in vitro

“…While it is also possible that the AKT-I acts by promoting the proliferation of C1 cells, we regard this as unlikely, as the AKT-I did not increase the expression of cell-cycle genes (Fig. 4F), a reliable means to infer cell cycle status (14,59,60). Coupled with our evidence that the AKT-I also does not act by promoting SPG survival (Fig.…”

Toxicological Effects of Cadmium on Mammalian Testis

“…Besides, in the fetus, SCs secrete anti-Müllerian hormone (AMH), which causes the regression of Müllerian duct (Unal et al, 2018). In the fetal life of rodents and humans, the number of SCs increases exponentially, and then slows down after birth and reaches adult levels in early puberty (Sharpe et al, 2003;O'shaughnessy et al, 2007;Guo et al, 2020;Tan et al, 2020).…”

Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells

“…In mice, male-specific GC development starts when PGCs colonize fetal testes and differentiate into prospermatogonia (also known as gonocytes), which divide several times as multiplying (M)-prospermatogonia (M) before becoming mitotically quiescent as primary transitional (T1)-prospermatogonia (T1). Immediately after the fetus is born, T1 migrate from the center of the seminiferous cords towards the periphery, which is the site of the spermatogonial stem cell (SSC) niche [7][8][9] . As they migrate, T1 proliferate and differentiate into secondary transitional (T2)prospermatogonia (T2).…”

“…As they migrate, T1 proliferate and differentiate into secondary transitional (T2)prospermatogonia (T2). T2 are considered the immediate precursors to SSCs, which are the founding population for establishing ongoing spermatogenesis 7,8 . Historically, male GCs at the prespermatogenesis (gonadal) phase have been referred to as PGCs, gonocytes, fetal spermatogonia, or prespermatogonia 8 .…”