AsianScientist (Mar. 8, 2012) – A*STAR scientists have discovered a link between a family of organic compounds called polyamines and embryonic stem cell (ESC) regulation.
In a paper published in this month’s issue of the journal Genes & Development, a team of scientists from A*STAR’s Institute of Medical Biology (IMB) showed the critical role of polyamines in ESC differentiation and self-renewal ability.
Polyamine are organic compounds with more than two amino groups (-NH2). Although the polyamine pathway is well-known and has been shown to be important in cancer and cell proliferation, its effects are less understood in ESC self-renewal.
The team found that high levels of Amd1 – an enzyme in the polyamine synthesis pathway – is essential for ESC to stay undifferentiated. When Amd1 levels were increased, ESC differentiation was delayed. Conversely, downregulation of Amd1 was necessary for differentiation of ESCs into neural precursor cells.
Another critical discovery was that Amd1 is translationally regulated by a micro-RNA (miRNA), the first ever demonstration of miRNA-mediated regulation of the polyamine pathway. This finding was made possible by a genome-wide screen in a mouse model to identify translational factors that controlled ESC differentiation to neural precursor cells.
Despite the great potential shown by ESCs to repair damaged tissues due to disease or trauma, one of the challenges is to control their differentiation into the right cell type, say the authors.
“It is possible that manipulation of polyamine levels in embryonic stem cells through inhibitors or activators of the pathway could help direct the differentiation of embryonic stem cells to more clinically useful cell types,” said lead author Dr. Leah Vardy, Principle Investigator at the IMB.
The next step is to understand in more detail the molecular targets of these polyamines in both ESCs and other cell types, Vardy said.
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