Stem cell factor affects fate determination of human gonocytes in vitro

Abstract

The stem cell factor (SCF), binding its tyrosine kinase receptor c-Kit, has been shown to play essential roles in the proliferation, differentiation, and survival of germline cells. However, few reports are available about the effect of SCF on the development of human gonocytes within the fetal testis. The objective of this study was to investigate whether SCF affects the biological behaviors of human gonocytes before or after they enter the mitotic arrest stage. Employing an organ culture system, we observed that addition of exogenous SCF could influence the morphology of human gonocytes in vitro. Moreover, SCF was able to trigger the colony formation of round gonocytes, which were characterized positive for alkaline phosphatase activity, Oct-4, SSEA-4, and c-Kit as well. We found that SCF exerted actions in a dose-and age-dependent manner, although the stimulatory effect lasted no more than 14 days. We also showed that SCF played a role in suppressing the apoptosis of human gonocytes. Blocking of SCF signaling with either phosphatidylinositol 3-kinase or mitogen-activated protein kinase inhibitor resulted in similar apoptotic features as well as the SCF-withdrawal cultures. Taken together, we report that SCF acts as a potent regulator in the fate determination of human gonocytes. Our studies should form the basis for in vitro studies and facilitate investigation of the molecular mechanisms underlying this unique stage. Reproduction (2007) 134 757-765

New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD)

“…PGCs are positive for the receptor, and the SCF will function as a chemo-attractant, leading the cells to the genital ridge, their final destination. This signalling pathway has various functions, including survival by preventing induction of apoptosis (Tu et al, 2007). Interestingly, disturbances in this signalling pathway result in various anomalies, including abnormal migration of PGCs, possibly leading to infertility.…”

Prevalence of c-KIT Mutations in Gonadoblastoma and Dysgerminomas of Patients with Disorders of Sex Development (DSD) and Ovarian Dysgerminomas

“…The ligand for c-KIT is the stem cell factor (SCF, KITLG) and the SCF-KIT pathway regulates the differentiation of melanocytes, red blood cells, mast cells, interstitial cells of Cajal, and germ cells [1], [2], [3]. Moreover, this pathway is important in the survival of primordial germ cells (PGCs) [4], [5]. Expression of c-KIT and gain-of-function mutations in c-KIT has been found in mastocytosis, leukemia and gastro-intestinal stromal tumors (GIST) [6], [7], [8].…”

Preimplantation Embryo Development and Primordial Germ Cell Lineage Specification

“…For example, adding LIF enhanced PGC survival, but the observations with the use of other factors is not as clear. [258][259][260] Currently, it is not at all clear that these cells resemble their germ cell counterparts in vivo, but improvements in culture conditions and the cellular microenvironment will certainly help in this regard. 256 However, a landmark study has recently shown that supplementation of LIF in a "2i" cocktail for mESC growth can induce an epiblast-like cell stage of mESCs and set the stage for PGC development.…”