Edinburgh Scientists Identify A Key Player In Making Specialised Cells From Embryonic Stem Cells

Main Category: Stem Cell Research
Article Date: 08 Feb 2006 - 14:00 PDT


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.

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".

These latest findings will also provide insights into some of the crucial differences between mouse and human embryonic stem cells. Mouse embryonic stem cells need the protein LIF to be able to make copies of themselves indefinitely; human embryonic stem cells, on the other hand, do not need LIF to keep multiplying. Mbd3-lacking cells are similar to human embryonic stem cells in that they do not require LIF. They may, therefore, be used as a tool to understand how human embryonic cells bypass the need for LIF when multiplying without limit.

Mbd3 is part of a large complex of proteins called the NuRD (Nucleosome Remodelling and Histone Deacetylation) complex. NuRD is known as an epigenetic silencer, as its role in cells is to turn genes off.

This research was supported by The Wellcome Trust, the MRC and the BBSRC.

The Institute for Stem Cell Research (ISCR) is a multidisciplinary research institute focused on molecular, cellular and developmental biology of stem cells. The ISCR's mission is to acquire an understanding of the mechanisms of stem cell self-renewal and differentiation processes and to provide scientific foundations for the application of cell replacement therapies in the treatment of human disease and injury. Further information on the ISCR is available at http://www.iscr.ed.ac.uk.

Stem cells glossary

Stem cell - an unspecialised cell that has the ability to multiply without limit, and can also give rise to specialised cell types in the body.

Embryonic stem cell - a stem cell originating from the early embryo that has the potential to make most cell types both in the body and in the laboratory.

Self-renewal - the ability of a stem cell to divide and produce copies of itself, for an indefinite period of time.

Epigenetics - chemical modifications to the DNA or the proteins with which DNA is packaged (called histones) that affect the activity a gene without changing the nucleotide sequence of the DNA.

Institute for Stem Cell Research
http://www.iscr.ed.ac.uk

Peer reviewed publication and references
Keisuki Kaji, Isabel Martin-Caballero, Ruth MacLeod, Jennifer Nichols, Valerie A. Wilson and Brian Hendrich (2006). The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nature Cell Biology DOI 10.1038/Ncb1372.

Link to published article:
dx.doi.org/10.1038/Ncb1372.

SOURCE: Nature Cell Biology
http://www.nature.com/ncb

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