Abstract
The most primitive germ cells in adult mammalian testis are the spermatogonial stem cells (SSCs) whereas primordial follicles (PFs) are considered the fundamental functional unit in ovary. However, this central dogma has recently been modified with the identification of a novel population of very small embryonic-like stem cells (VSELs) in the adult mammalian gonads. These stem cells are more primitive to SSCs and are also implicated during postnatal ovarian neo-oogenesis and primordial follicle assembly. VSELs are pluripotent in nature and characterized by nuclear Oct-4A, cell surface SSEA-4, and other pluripotent markers like Nanog, Sox2, and TERT. VSELs are considered to be the descendants of epiblast stem cells and possibly the primordial germ cells that persist into adulthood and undergo asymmetric cell division to replenish the gonadal germ cells throughout life. Elucidation of their role during infertility, endometrial repair, superovulation, and pathogenesis of various reproductive diseases like PCOS, endometriosis, cancer, and so on needs to be addressed. Hence, a detailed review of current understanding of VSEL biology is pertinent, which will hopefully open up new avenues for research to better understand various reproductive processes and cancers. It will also be relevant for future regenerative medicine, translational research, and clinical applications in human reproduction.
Highlights
Stem cells have the capacity to self-renew as well as give rise to differentiated progeny
It was postulated that spermatogonial stem cells (SSCs) undergo dedifferentiation and result in ES-like colonies in vitro [13], but recent studies from our group demonstrated the presence of pluripotent, very small embryonic-like stem cells (VSELs) with high nucleocytoplasmic ratio and nuclear Oct-4 in adult human testis [19] and ovary for the first time [17]
We propose that rather than dedifferentiation of SSCs as earlier postulated, it may be possible that the VSELs per se expand to give rise to ES-like colonies in vitro [20]
Summary
Stem cells have the capacity to self-renew as well as give rise to differentiated progeny. Zou et al [18] successfully cultured female germline stem cells derived from both neonatal and adult ovary for several months in vitro, which when transplanted in busulfan treated mice led to the birth of normal pups This demonstrated supremacy of the gonadal stem cells differentiated by the in vivo cues over in vitro manipulated ES cells to generate synthetic gametes. It was postulated that spermatogonial stem cells (SSCs) undergo dedifferentiation and result in ES-like colonies in vitro [13], but recent studies from our group demonstrated the presence of pluripotent, very small embryonic-like stem cells (VSELs) with high nucleocytoplasmic ratio and nuclear Oct-4 in adult human testis [19] and ovary for the first time [17]. As they become scarce with age, regeneration becomes inefficient resulting in age-related disease manifestations
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