After a sperm fertilizes an egg, the cells of the resulting zygote begin dividing continuously, eventually growing into a fetus. The zygote and its first two “daughter” cells are considered to be totipotent, meaning they can become any of the cell types in an organism, including those of the placenta and fetus. But shortly thereafter, between the 8- to 32-cell stages, some of the cells become destined to develop only into placental cells and others only into fetal cells.
Cells that can become any fetal cell type—called pluripotency—are called embryonic stem (ES) cells. ES cells cannot, for the most part, become placental cells. However, in a culture of ES cells, scientists in the Unit on Mammalian Epigenome Reprogramming, within the Division of Intramural Research Program in Genomics of Differentiation, found that a few cells (between 0.2% and 1.5%) more closely resembled totipotent cells at the two-cell zygote stage than normal ES cells in terms of epigenetics. Of particular importance, this “two-cell-like” state within ES cells was controlled by the regulatory activity of retroviruses embedded near important developmental genes.
The researchers also found that, at some point, most ES cells fluctuated between this two-cell-like state and the normal ES cell state. Finally, the researchers established that the two-cell-like ES cells were capable of becoming any cell type of either placental or fetal tissue. The scientists suggested that ES cells fluctuate through these different states in order to rejuvenate the chromatin that packages DNA and maintain its integrity as the organism undergoes the crucial first steps of development.
These findings have added important new information to scientists’ understanding of the evolution of pregnancy and early development in mammals (PMID: 22722858).