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Scientific news

Stem cells: The role of MOF and its complexes

The different action of NSL and MSL complexes on ES cells genome.

Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation.

Ravens S(1), Fournier M(1), Ye T(2), Stierle M(1), Dembele D(2), Chavant V(3), Tora L(1).

Elife June 4, 2014


June 4, 2014

The team of Laszlo Tora has just highlighted the roles of an enzyme, MOF, in both complexes MSL and NSL, in the growth and differentiation of embryonic stem cells. Published in the journal eLife on June 4th 2014, these results push the frontiers of knowledge on these cells with a very great therapeutic potential.

 

Embryonic stem cells are "pluripotent" cells derived from an early embryo. Actually, they are able to differentiate into multiple cells with radically different functions (neurons, muscle or skin cells, etc.). Their therapeutic potential is huge, since this property would give them the power to regenerate or repair damaged or diseased organs, which explains the current enthusiasm of researchers to better understand the special features of these cells.

 

In this new study, the team of Laszlo Tora focused on the MOF enzyme, already known to be essential for embryonic stem cells, both for the maintenance of pluripotency, but also to trigger their differentiation into specialized cells. This enzyme is a subunit of two protein complexes, MSL and NSL. The researchers got interested in the respective roles of these two complexes in the maintenance of embryonic stem cells and their differentiation. With the technique of ChIP-seq, researchers were able to determine the binding sites of these complexes throughout the genome of stem cells, comparing them with the modulation of expression of downstream genes. They demonstrated that they had an action on common sites but that their binding was mainly localized on different genes. Thus, the researchers found that NSL primarily bound on the constituent genes (genes expressed in the same way in all cells of an organism), while MSL stimulated more genes involved in differentiation. Moreover, they showed that NSL was fixed exclusively on promoters while MSL more targeted the middle of genes.

 

This study provides new evidence for the understanding and control of embryonic stem cells and suggests new hopes for the use of these cells for therapeutic purposes.

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