Authentic embryonic stem cells are defined by three cardinal properties: unlimited symmetrical self-renewal in the lab; comprehensive contribution to primary chimeras; and generation of functional egg and sperm for genome transmission. Chimeras are produced when embryonic stem cells are inserted into a developing blastocyst and those stem cells go on to contribute to a normal embryo with cells of two origins, Ying explained. Because those embryonic stem cells can contribute to the germ line, any genetic alterations they carry such as the loss or gain of a gene--can be passed on to the next generation.
The versatility of embryonic stem cells, combined with the ease with which they can be manipulated genetically, has provided a powerful means to elucidate gene function and create disease models via the generation of transgenic, chimeric, and knock-out animals. Although embryonic stem cells have been routinely derived from particular strains of mice since 1981, their capture from rats or other animals had remained elusive.
While human embryonic stem cell lines do exist, Ying said, it's not clear that they represent the most grounded stem cell state because the essential properties can't be demonstrated for obvious ethical reasons.
Now, Ying and Smith's teams show that a two- or three-ingredient concoction known as 2i or 3i respectively, which inhibits signals that would otherwise activate the differentiation process, maintains rat embryonic stem cells in their natural default state, allowing them to self-renew, or multiply, as generic stem cells. (The cocktails include inhibitors of GSK3, MEK, and FGF receptor tyrosine kinases.)
Most importantly, the isolated cells can produce high rates of chimerism when reintroduced into early stage embryos and can transmit through the germline, they report.
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|Contact: Cathleen Genova|