Scientists from the University of Edinburgh have shown that the protein Mbd3 plays a crucial role in the process by which embryonic stem cells become specialised cells, such as brain or skin cells. These findings make significant advances in understanding how embryonic stem cells can be made to become all the different types of cell in the body, ultimately to be used in replacement therapies for specific diseases and injuries. This research is published online this week in the leading scientific journal Nature Cell Biology.
Mouse embryonic stem cells can be directed to become neurons (green) when grown in a dish…
...but when Mbd3 is lacking most cells remain as embryonic stem cells (red).
In the body, stem cells divide to produce both copies of themselves and other, more specialised, cell types. The Edinburgh scientists made mouse embryonic stem cells lacking the Mbd3 protein. Unlike non-engineered cells, the Mbd3-lacking cells failed to form different cell types when induced to do so in a dish, but rather remained in an uncommitted state. When injected into very early mouse embryos, the Mbd3-lacking cells behaved in a similar way, disrupting the normal development of the embryo.
Brian Hendrich, leading the research team, says “It is well established that embryonic stem cells need certain factors to sustainably make copies of themselves, that is, to self-renew. We have now shown, for the first time, that to leave that state and go down the specialisation pathway cells require the activity of Mbd3; it is not enough simply to remove the self-renewal factors. If Mbd3 is absent, the cells remain in an embryonic stem cell-like state”.
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