They adapt to changing environmental conditions. Embryos develop in a predictable manner toward a species-specific adult form (human embryos do not mature into mice, monkeys, or tumors). While stem cells, tumors, and embryos have many molecular features in common, embryos are clearly organisms. Consequently, a cell that is totipotent is also a one-cell embryo that is, a cell that is capable of generating a globally coordinated developmental sequence. Totipotency in this strict sense is demonstrated by the ability of an isolated cell to produce a fertile, adult individual. Producing a mature organism requires the ability to both generate all the cells of the body and to organize them in a specific temporal and spatial sequence, that is, to undergo a coordinated process of development. The difference between these two definitions is not trivial. A one-cell embryo (zygote) is “totipotent” in both senses yet, some authors characterize tumors and stem cells as “totipotent,” based only on the second definition (ie, the ability of these cells to produce a wide range of cell types). Much of the confusion surrounding the term totipotency centers on the important differences between these two definitions. T he medical dictionary administered by the National Institutes of Health gives two contrasting definitions for the term totipotent: “capable of developing into a complete organism” or “differentiating into any of its cells or tissues” ( accessed ). Finally, the implications of twinning for our understanding of totipotency are discussed. The requirement for specific, oocyte-derived cytoplasm as a component of totipotency is outlined. A new term, “plenipotent,” is proposed to resolve this confusion. Here, the concept of totipotency is discussed, and the confusions surrounding this term in the scientific and nonscientific literature are considered. In this context, clarifying precisely what is meant by “totipotency” and how it is experimentally determined will both avoid unnecessary controversy and potentially reduce inappropriate barriers to research. Ethical controversy surrounding an area of research can have a chilling effect on investors and industry, which in turn slows the development of novel medical therapies. Increasingly, ethical objections to scientific research have both practical and political implications. This increases the potential applications of regenerative medicine, especially in cell replacement therapies.Īccording to Assistant Professor Tee Wee Wei, the lead investigator in this study, the eventual goal of this research is to translate the findings into the development of rapid and efficient cellular reprogramming strategies for clinical application, such as in the treatment of debilitating diseases and developmental disorders.There is surprising confusion surrounding the concept of biological totipotency, both within the scientific community and in society at large. All these changes will result in pluripotent stem cells reverting into a totipotent-like state.ĭiscovering this method of inducing totipotency in cells outside of the embryo also provides a means to engineer cells with maximum cell plasticity for therapeutic purposes. NELFA is also able to alter the energy using pathways in the pluripotent stem cells. Specifically, NELFA has the ability to reactivate certain genes that are only active in the zygote but otherwise silent in embryonic stem cells. NELFA achieves this feat by causing specific changes in the gene regulatory and metabolic networks of the cell. The study identified a totipotency-inducing factor - Negative Elongation Factor A (NELFA), which is capable of driving pluripotent embryonic stem cells into totipotency in a petri dish. This not only provides key insights into how totipotency is formed and the earliest events in mammalian development, but opens new doors for potential cell therapies that were previously unexplored. Scientists at the National University of Singapore's Yong Loo Lin School of Medicine have now found a way to manipulate pluripotent cells into acquiring the totipotent capacity previously thought to exist only in the zygote. Surpassing pluripotent embryonic stem cells, which are only able to differentiate into all cell types within the embryo, the totipotent zygote loses its totipotency as in matures into pluripotency. Totipotent cells sit atop the developmental hierarchy and have the greatest potency of all cell types, giving it limitless therapeutic potential.
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