Effects of paracrine factors on CD24 expression and neural differentiation of male germline stem cells

Abstract

Spermatogonial stem cells (SSCs) are adult male germ cells that develop after birth. Throughout the lifetime of an organism, SSCs sustain spermatogenesis through self-renewal and produce daughter cells that differentiate into spermatozoa. Several studies have demonstrated that SSCs can acquire pluripotency under appropriate culture conditions, thus becoming multipotent germline stem cells (mGSCs) that express markers of pluripotency in culture and form teratomas following transplantation into immunodeficient mice. In the present study, we generated neural precursor cells expressing CD24, a neural precursor marker, from pluripotent stem cell lines and demonstrated that these cells effectively differentiated along a neural lineage in vitro. In addition, we found that paracrine factors promoted CD24 expression during the neural differentiation of mGSCs. Our results indicated that the expression of CD24, enhanced by a combination of retinoic acid (RA), noggin and fibroblast growth factor 8 (FGF8) under serum-free conditions promoted neural precursor differentiation. Using a simple cell sorting method, we were able to collect neural precursor cells with the potential to differentiate from mGSCs into mature neurons and astrocytes in vitro.

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes

“…Our results further revealed excellent safety and efficacy in a rodent model of PD using SSC-derived DA neurons, which may be due to direct induction without the introduction of ectopic genes. This finding has also been supported by our previous reports [20]. Thus, the present study may provide an implication for the application of SSC-based therapeutic covering a vast array of regenerative medicine disciplines.…”

The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas

“…In conclusion, CD24 has a bivalent function in regulating developmental and differentiation processes by negatively and positively regulating glycoproteins; that is, it blocks the germ cell program and mesodermal differentiation and is able to poise cells for ectodermal differentiation. In line, CD24 ‐expressing neural precursor cells generated from pluripotent stem cells effectively differentiated along the neuronal lineage in vitro [95].…”

Application of microfluidic systems for neural differentiation of cells

“…[12] Small molecules may include GFs, ECM components, cytokines, and vitamin derivatives which their incorporation in different processes may accelerate the differentiation of stem cells. Some of the frequently used stimulant molecules are retinoic acid (RA), [13,14] ascorbic acid, [15] basic fibroblast growth factor (bFGF), [16] nerve growth factor (NGF), [17] and insulin-like growth factor (IGF-I). [18] Although these macroscopic cell culture dishes are widely utilized with standard protocols and are relatively easy to set up, they face some limitations in practice including the rigid cell culture surface, stagnant culture media, fixed device architecture, difficult to achieve perfusion, and chemical gradients.…”