Abstract
Sertoli cells are required for normal spermatogenesis and they can be reprogrammed to other types of functional cells. However, the number of primary Sertoli cells is rare and human Sertoli cell line is unavailable. In this study, we have for the first time reported a stable human Sertoli cell line, namely hS1 cells, by overexpression of human telomerase. The hS1 cells expressed a number of hallmarks for human Sertoli cells, including SOX9, WT1, GDNF, SCF, BMP4, BMP6, GATA4, and VIM, and they were negative for 3β-HSD, SMA, and VASA. Higher levels of AR and FSHR were observed in hS1 cells compared to primary human Sertoli cells. Microarray analysis showed that 70.4% of global gene profiles of hS1 cells were similar to primary human Sertoli cells. Proliferation assay demonstrated that hS1 cells proliferated rapidly and they could be passaged for more than 30 times in 6 months. Neither Y chromosome microdeletion nor tumorgenesis was detected in this cell line and 90% normal karyotypes existed in hS1 cells. Collectively, we have established the first human Sertoli cell line with phenotype of primary human Sertoli cells, an unlimited proliferation potential and high safety, which could offer sufficient human Sertoli cells for basic research as well as reproductive and regenerative medicine.
Highlights
Sertoli cells are essential for normal spermatogenesis which comprises the mitosis of spermatogonial stem cells, the meiosis of spermatocytes, and the spermiogenesis of haploid spermatids
Microarray analysis showed that 70.4% of global gene profiles of hS1 cells were similar to primary human Sertoli cells
We found that there was no significant difference in the expression of GATA4, glial cell derived neurotrophic factor (GDNF), SOX9, GATA1 and WT1 between the immortalized human Sertoli www.impactjournals.com/oncotarget
Summary
Sertoli cells are essential for normal spermatogenesis which comprises the mitosis of spermatogonial stem cells, the meiosis of spermatocytes, and the spermiogenesis of haploid spermatids. The tight junction, constituted by Sertoli cells, is the key structure of the blood-testis barrier (BTB) to ensure the stabilization of the microenvironment or niche of the testis. E.g., zona occludens 1 (ZO1), claudin 11 (CLDN11)[2], and occluding (OCLN), are produced by Sertoli cells, and they play vital roles in controlling the function of BTB[3]. In addition to structural support, Sertoli cells play significant roles in promoting the self-renewal, differentiation, and apoptosis of spermatogonial stem cells via secreting a number of growth factors, including bone morphogenetic protein 4 (BMP4), stem cell factor (SCF), leukemia inhibitory factor (LIF), glial cell derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), and epidermal growth factor (EGF) [1].
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