Scientists "reset" human pluripotent stem cells to the earliest stage of development, equivalent to an embryo that is only between seven and nine days old.
The cells could help mark the true starting point of human development, and have been impossible to replicate in the lab until now, the University of Cambridge reported. The finding could help researchers gain a better understanding of human development and could lead to better cell therapies.
Human pluripotent stem cells can transform into any cells in the body's tissues; they can be made in lab either from cells extracted from an embryo or from adult cells that have been reverted to the pluripotent stage. In the past researchers worked to generate pluripotent stem cells that are "pristine," (naïve)as an alternative the research team derived cells that were slightly more advanced. These cells still hold many of the early abilities to differentiate into distinct cell types, but are not truly at a "blank" state. This could explain why pluripotent cells often exhibit a tissue bias in lab settings.
In the recent study researchers induced a ground state by "rewiring the generic circuitry" in human embryonic and pluripotent stem cells. These reset cells are believed to share many of the characteristics of naïve embryonic cells in mice, suggesting they represent the earliest stage of development.
"Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues," said Professor Austin Smith, Director of the Stem Cell Institute, who co-authored the paper. "Scientists have perfected a reliable way of doing this with mouse cells, but human cells have proved more difficult to arrest and show subtle differences between the individual cells. It's as if the developmental clock has not stopped at the same time and some cells are a few minutes ahead of others."
Mouse cells can be frozen in a state of naïve pluripotency using a protein called LIF, but human cells are not as responsive to this method. The team overcame this problem by introducing two genes called NANOG and KLF2. This triggered the network of genes that controlled the cell to reboot and induce the naïve pluripotent state. These genes need only be present for a short period of time.
"Our findings suggest that it is possible to rewind the clock to achieve true ground state pluripotency in human cells. These cells may represent the real starting point for formation of tissues in the human embryo. We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people," Smith said.
The findings were published in a recent edtion of Cell.
