The team found that when human embryonic stem cells are cut out from the colony, this key protein is disrupted and then internalized within the cell. Without e-cadherin on the cell surface, cell signaling between the cells and their environment is disrupted and the cells quickly die.
Both chemical compounds identified by the study, however, protected e-cadherin from damage.
In further experiments, the scientists found that the key difference between human and mouse embryonic stem cells lay not only within the cells themselves, but also in and controlled by their microenvironmentthe surrounding cells, signaling factors, and extracellular matrix. The scientists were able to transfer human embryonic stem cells into a mouse embryonic stem cell microenvironment. There, the scientists found, human cells were more likely to survive, even without the survival-promoting compounds.
Moreover, when the scientists chemically induced human embryonic stem cells back to an earlier stage of developmentwhich had an extracellular environment similar to mouse embryonic stem cells conventionally used in the laboratorythere were also no longer problems growing them in culture.
"This validated our mechanistic investigations from a different angle," said Ding, "showing that we had dissected out a very core regulatory mechanism."
Ding expects that the methods discussed in the new study will soon be widely adopted by stem cell laboratories around the world.
"My lab currently uses the novel small molecules indentified in this study on a routine basis, making our life significantly easier and advancing our efforts," said Ding. "Even more, chemically inducing human embryonic stem cells back to an earlier stage of development has advantages for some areas of investigation."
|Contact: Keith McKeown|
Scripps Research Institute