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Self-renewal and differentiation of spermatogonial stem cells

differentiation, dedifferentiation, and transdifferentiation of SSCs and their potential applications in regenerative and reproductive medicine. Spermatogonial stem cells undergo self-renewal to maintain the stem cell pool while they differentiate into sperm in mammalian testis. Spermatogonia are classified into three types, including type A, intermediate, and type B cells, based upon their morphological characteristics. 19 Type A spermatogonia can be subdivided into A single (A s), A paired (A pr) and A aligned (A al) cells. SSCs are very rare, with only approximately 0.02%–0.03% of all germ cells in adult testis; 22 nevertheless, thousands of spermatids are produced each day, reflecting an unlimited potential of SSC division and differentiation. We illustrated the self-renewal and differentiation of the rodent and human SSCs in Figure 1. In rodents, A s spermatogonia can divide symmetrically to produce new A s stem cells or they divide asymmetrically to give rise to A s spermatogonia and A pr spermatogonia that are characterized by an intercellular cytoplasmic bridge. The A pr spermatogonia continue to divide and form chains of A al spermatogonia (4, 8, 16, and 32 cells) that are able to differentiate into type A 1 to A 4 , intermediate (In) and B spermatogonia. Type B spermatogonia further differentiate to primary spermatocytes, secondary spermatocytes, and eventually spermatids via two meiotic divisions. There are distinct cell types and biochemical phenotypes between rodent and human male germline stem (GS) cells. INTRODUCTION The pluripotent properties of stem cells have attracted considerable interest in both basic research and clinical applications.