The endocytic protein asrij regulates pluripotency in mouse embryonic stem cells

Abstract

For a long time an intriguing and puzzling aspect in biology is the development of a multicellular organism from a single cell. Mammalian development is carefully organized and orchestrated to transit from a single celled zygote to a spectrum of somatic and germ cells present in the body (Dejosez and Zwaka, 2012). It is of paramount importance to elucidate the molecular regulatory mechanisms behind this process, not only to understand basic development better, but also, to improve aspects of therapeutic medicine. As the mammalian embryo develops it undergoes rounds of cell division, termed as cleavage, to expand the number of cells without any increase in cytoplasmic mass. With successive divisions the potency of embryonic cells gets restricted, cell fate is specified and by the thirty two cell stage in mouse embryos, there is a clear demarcation between two different populations in the embryo. The outer trophoectoderm layer goes on to form the placental structures and the inner group of 12-15 cells, known as inner cell mass (ICM), gives rise to all the somatic and germ cells in the adult (Gilbert, 2006; Nichols and Smith, 2009). The ICM cells can give rise to all the lineages because they are pluripotent in nature, a property which is transient in vivo but the same cells can be captured in vitro and cultured for indefinite period of time while keeping them pluripotent (Evans and Kaufman, 1981; Martin, 1981). These ICM derived cells capable of long term culture are known as embryonic stem cells (ESCs) and they differ from any other somatic stem cells in mainly two aspects. ESCs can self renew for an indefinite time period and this is achieved by symmetric cell division in which, both the daughter cells have equal potency similar to the mother cell (Chambers and Smith, 2004). In contrast, adult stem cells can self renew only by asymmetric cell division, where one daughter cell replenishes the pool and the other one differentiates to a pre-determined lineage (Neumuller and Knoblich, 2009). Another striking difference between the two stem cell types is the property of ESCs to give rise to all the cells of an organism (Solter, 2006), while adult stem cells can only give rise to a handful of cell types. Due to these two properties ESCs are the best in vitro model system to study and understand the mechanism of early development.