Epigenetic control centre times development of placental tissue

The correct propagation and differentiation of stem cells is crucial for healthy embryonic development.

A Freiburg research team has now succeeded in demonstrating that epigenetic modifiers regulate the timely formation of the placental tissue, thus guaranteeing the balance between undifferentiated and differentiated cells. The team’s findings were published in the renowned journal .

The research group, led by Prof. Dr. Roland Schüle, Director of Central Clinical Research at the Freiburg University Medical Center and member of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg, is investigating initial cellular differentiation in mammalian development. The blastocyst develops out of the unfertilized egg cell within the space of only a few days. It consists of two layers: While the inner cell mass is where the fetus itself develops, the outer cell layer – the trophectoderm – is where auxiliary organs such as the placenta and egg membranes form. In order for this to happen, the trophoblast stem cells must develop into particular cell types. Tight regulation of the propagation and differentiation of these stem cells guarantees that a sufficient amount of cells is available for the formation of the placental tissue, while at the same time maintaining a reservoir of stem cells.

The stem cell researchers studied how epigenetic modifiers regulate the differentiation of the trophoblast stem cells. They were particularly interested in observing the function of the so-called lysine-specific demethylase 1 (Lsd1), which proved to be the central gatekeeper for the correct time of differentiation. The scientists succeeded in demonstrating that Lsd1 suppresses the transcription factor Ovol2 in the as yet undifferentiated cells, thus preventing them from differentiating, migrating, and invading the maternal decidua prematurely. At the same time, Lsd1 determines what cell type the trophoblast stem cells differentiate into.

Further experiments demonstrated that a deficiency of Lsd1 leads to a decrease in the number of trophoblast stem cells, a reduction in the formation of tissue, and thus to the premature death of the embryo. Therefore, Lsd1 maintains the balance between undifferentiated and differentiated cells, making a key contribution to the success of embryonic development.

Original publication:

Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells.
Zhu D, Hölz S, Metzger E, Pavlovic M, Jandausch A, Jilg C, Galgoczy P, Herz C, Moser M, Metzger D, Günther T, Arnold SJ, Schüle R.
Nat Commun. 2014 Jan 22;5:3174

http://www.nature.com/ncomms/2014/140122/ncomms4174/full/ncomms4174.html