Stem cells are characterized by their self-renewal potential and ability to differentiate into various cell lineages (pluripotency or multipotency) or one specific cell lineage (unipotency). Stem cells can be obtained directly from organs or induced to exhibit stem cell properties in culture. Based on the origins of the stem cells, at least three major types of stem cells have been categorized: embryonic stem (ES) cells, germ-line-derived stem cells, and adult somatic stem cells. ES cells, which are derived from the inner cell mass of blastocysts, are innately pluripotent with the capacity to differentiate into cells of all three germ layers. Germ-line-derived stem cells can be induced either from embryonic primordial germ cells or from spermatogonial stem cells (SSCs) of the neonate, juvenile or adult testis. While SSCs are normally unipotent when they reside within the seminiferous epithelium, they can be induced to pluripotency in vitro
or after transplantation into a different niche microenvironment (1
). Adult somatic stem cells, also known as non-embryonic somatic stem cells, are obtained from adult tissues such as bone marrow and their differentiation ability (multipotency) is more restricted as compared to ES cells. Recently, a novel source of pluripotent stem cells (iPS) was established by reprogramming fibroblasts or other somatic cells to pluripotency through ectopic expression of defined transcription factors (2
). In this review, we focus specifically on whether different cell types of the gonads have stem cell properties and the implication of these findings for stem cell research.
The gonadal primordium (or genital ridge) is the only primordium that has the potential to differentiate into two distinct organs (testis or ovary). In mammals, presence or absence of the Sry gene (Sex-determining gene of the Y chromosome) activates and/or inhibits molecular programs in the gonadal primordium, directing the differentiation program toward testis organization (7
). The sex-determining programs operate mainly in the somatic cell lineages in the gonadal primordium and the somatic environment eventually decides the developmental fate of primordial germ cells (PGCs). In mouse embryos, epiblast-derived PGCs migrate through the hindgut into the gonadal primordium between embryonic day 9–11.5 or E9–11.5 (8
). Meanwhile, the coelomic epithelium surrounding the gonadal primordium starts to thicken and, under the control of a network of transcription factors, precursors of somatic cell lineages arise (10
). In the male gonad, under the control of Sry, somatic cell precursors differentiate into Sertoli cells, Leydig cells, and peritubular myoid cells. On the other hand in the ovary, granulosa and theca cell lineages appear as the ovarian follicles start to assemble. PGCs and spermatogonia in testes have stem cell properties and are able to differentiate into other cell types under certain conditions (11
). We will discuss whether other cell types in the gonads also possess such ability.