Totipotency (Lat. totipotentia, "ability for all [things]") is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.
In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential, being able to differentiate into any embryonic cell, as well as extraembryonic cells. In contrast, pluripotent cells can only differentiate into embryonic cells.
It is possible for a fully differentiated cell to return to a state of totipotency. This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency. Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in mouse embryonic stem cell cultures and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.
The human development model is one which can be used to describe how totipotent cells arise. Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote. In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), or into cells of the placenta (cytotrophoblast or syncytiotrophoblast). After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.
Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species. Work with zebrafish and mammals suggest a further interplay between miRNA and RNA-binding proteins (RBPs) in determining development differences.
Primordial germ cells
In mouse primordial germ cells, genome-wide reprogramming leading to totipotency involves erasure of epigenetic imprints. Reprogramming is facilitated by active DNA demethylation involving the DNA base excision repair enzymatic pathway. This pathway entails erasure of CpG methylation (5mC) in primordial germ cells via the initial conversion of 5mC to 5-hydroxymethylcytosine (5hmC), a reaction driven by high levels of the ten-eleven dioxygenase enzymes