Human embryonic stem cells offer the possibility to treat a variety of diseases since these nascent cells can differentiate into any type of mature cell. Equally important, knowing how to preserve hESCs in their pluripotent state until that change is needed will help scientists better harness these cells for use in a variety of therapies.
A key gene receptor and signaling pathway identified by researchers from the University of California, San Diego School of Medicine plays an essential role in preserving hESCs in an undifferentiated state. The findings, published this week in the Proceedings of the National Academy of Sciences, also point to a possible new target for attacking cancer stem cells.
The WNT signaling pathway, a large family of genes known as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7, are the focus of the research.
"WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state," said Karl Willert, an assistant professor in the department of cellular and molecular medicine at UCSD, in a statement. "If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state."
To prove this, researchers used an antibody-like protein that binds to FZD7 to block its function. This prevented hESCs' ability to receive the WNT signal essential to maintaining their undifferentiated state, demonstrating that the WNT pathway needs to be "open" to hold cells in their nascent state.
FZD7 is known as an "onco-fetal protein," meaning it is expressed only during embryonic development and by certain human tumors. Previous research has suggested that FZD7 may be a biomarker for cancer stem cells and helps promote tumor growth. Willert said disrupting FZD7 function in cancer cells could potentially halt their development and growth, similar to how it works in hESCs.
The researchers plan to do further testing on their FZD7-blocking compound as a potential cancer treatment.
- read the press release
- check out the study abstract