A defining characteristic of stem cells is that they are able to self-renew by cell division for prolonged periods while maintaining the ability to differentiate into multiple cell types. A new study in the January issue of Nature Cell Biology, finds that p53 - known for its master regulatory role as a tumor suppressor - can also switch off self-renewal and initiate differentiation in mouse embryonic stem cells. Given p53's ability to sense toxic insults and DNA damage, these findings suggest that p53 may protect the genetic stability of stem cells by inducing differentiation and subsequent cell death of defective stem cells.
p53 mediates most of its effects by regulating the expression of genes. Xu and colleagues, found that p53 turned off the Nanog gene, which is known to be necessary for self-renewal of embryonic stem cells. Loss of Nanog leads to the differentiation of the embryonic stem cells. Nanog is known to be important for regulating stem cell proliferation in the early embryo, but it is unclear at this point whether or not its regulation by p53 is important for early development.
The therapeutic potential of human embryonic stem cells has generated a lot of interest into the molecular machinery that regulates their self renewal, and these findings identify an important new player for investigation.
Yang Xu (University of California, San Diego, La Jolla, CA, USA)
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(C) Nature Cell Biology press release.
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