CAMBRIDGE, Mass. (July 24, 2014) For years, researchers and patients have hoped that embryonic stem cells (ESCs)capable of forming nearly any cell type in the bodycould provide insight into numerous diseases perhaps even be used to treat them. Yet progress has been hampered by the inability to transfer research and tools from mouse ESC studies to their human counterparts, in part because human ESCs are "primed" and slightly less plastic than the mouse cells.
Now Thorold Theunissen, Benjamin Powell, and Haoyi Wang, who are scientists in the lab of Whitehead Institute Founding Member Rudolf Jaenisch, have discovered how to manipulate and maintain human ESCs in a "nave" or base pluripotent state similar to that of mouse ESCs without the use of any reprogramming factors. Their work is described in this week's issue of the journal Cell Stem Cell.
Nave mouse ESCs are well-studied, and scientists have a strong understanding of how they function and mature into more specialized cells. But this understanding is of limited use in human ESC research, as the human cells look different, grow differently, and rely on different genes than mouse ESCs. According to Theunissen, the disparities between mouse and human ESCs are attributable not to species-specific differences but rather to differences of cell state.
In nave mouse ESCs, a particular enhancer of the gene OCT4 is active, prompting the researchers to look for the presence of this marker as a means to identify rare nave human ESCs. With this unbiased reporter system in hand, the Jaenisch team determined that a cocktail of five small molecules with a few additional growth factors can induce and support the conversion of primed human ESCs to a nave state with or without using reprogramming factors to jumpstart the process.
By applying this cocktail to human blastocysts, the scientists could also isolate nave human stem cells.
"This is important because if this cockt
|Contact: Nicole Giese Rura|
Whitehead Institute for Biomedical Research