Plasticity of spermatogonial stem cells

Abstract

There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine.

Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis

“…Thus, adult rSLCs form functional prostatic epithelium expressing normal histological and molecular characteristics when combined with fetal mouse UGM. These findings are similar to previous results showing that UGM recombined in heterotypic tissue recombinations with urinary bladder or vaginal epithelium (Cunha, 1975; Cunha et al , 1980; Cunha et al , 1983a) or spermatogonial stem cells (Simon et al , 2009; Cooke et al , 2015) could induce prostatic epithelial differentiation in these cells.…”

“…The ability of rSLCs to differentiate into UtE under the inductive influence of neonatal UtM is similar to heterotypic tissue recombinations that have been reported previously for neonatal UtM recombined with neonatal vaginal epithelium (Cunha, 1976; Kurita et al , 2001), spermatogonial stem cells (Simon et al , 2009; Cooke et al , 2015) or aorta-derived mesangioblasts (Simon et al , 2013), all of which form morphologically and functionally normal uterine epithelium. Thus, various differentiated cell types can transdifferentiate into UtE expressing key markers for this tissue under the inductive influence of neonatal UtM.…”

“…Prostatic epithelium in tissue recombinants is derived from the GFP − rSLCs used in these grafts, as UGM grafts alone form only fibromuscular tissue as previously reported (Cunha et al , 1992). Critically, prostatic epithelium in GFP + -UGM + SLC grafts, control GFP − -UGM + GFP + -UGE grafts and host prostate all robustly expressed NKX3.1, an important marker of prostatic epithelium not expressed in Leydig cells or other testicular cell types (Simon et al , 2009; Cooke et al , 2015). Mouse NKX3.1 is a homeobox transcription factor that induces prostatic epithelial differentiation and is essential for normal prostate ductal branching and secretory protein production (Tanaka et al , 2000).…”

“…This suggests that adult rSLCs have restricted plasticity compared to other stem cells such as spermatogonial stem cells (Simon et al , 2009; Cooke et al , 2015), which are capable of differentiating into epithelium from all germ layers. Similar to rSLCs, aorta-derived mesangioblasts also did not transdifferentiate into epidermis (Simon et al , 2013).…”

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

“…GC-1spg cells, a mouse spermatogonia-derived cell line, represent the differentiation state of type B spermatogonia or preleptotene spermatocytes [1,37]. Several studies have demonstrated GC-1spg cell plasticity [1,4,78,79]. In our study, we drove BMP9 expression using a recombinant adenovirus.…”