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A new player inducing pluripotent cell fate in early development

At 4-cell stage, cells that express PRDM14 tend to become the future embryonic cells, while the others will become cells from the future placenta. ©Sandra Bour


Single-Cell Profiling of Epigenetic Modifiers Identifies PRDM14 as an Inducer of Cell Fate in the Mammalian Embryo.

Burton A, Muller J, Tu S, Padilla-Longoria P, Guccione E, Torres-Padilla ME.

Cell Rep Nov. 14, 2013


Oct. 31, 2013

During embryonic development, DNA undergoes dramatic changes that will guide the cells toward different cell fates. Maria-Elena Torres-Padilla’s team at the IGBMC reveals that PRDM14 is a novel player involved in the implementation of changes in the DNA at a very early stage of development. This process is responsible for the development of some of the cells of the embryo that give rise to embryonic stem cells. These results were published Oct. 31 in the journal Cell Reports.

 

Three and a half days after fertilization, a structure emerges from the apparently unorganized cell mass in the mouse embryo. It becomes a structured set of two cell types. This stage is named blastocyst and takes place right before implantation in the uterus of the mother. The two different types of cells will form respectively the embryonic stem cells at the origin of all future cells of the organism and the placenta, which will allow the mother to nourish the embryo during gestation.  Since the discovery of embryonic stem cells in the 80s, researchers seek to understand the molecular mechanisms which regulate the formation of such pluripotent cells.

 

In previous work, Maria-Elena Torres-Padilla’s team at IGBMC had shown that some changes on the chromatin are involved in the early development of the mouse embryo. These modifications, sometimes referred to as epigenetic, can change the level of chromatin compaction and thus regulate the expression of genes that govern the cell fate. In this new study, researchers became interested in the proteins that carry out these changes on the chromatin. They analysed 43 chromatin modifier proteins. Using microfluidics, an innovative technology at the interface between physics and biology, the researchers were able to observe the expression of these 43 different genes within a single living cell.

 

The researchers identified two distinct groups of genes expressed in the two types of cells of the blastocyst. In particular, the gene PRDM14 is highly expressed in the future embryonic stem cells. This asymmetry is also observed at a very early stage of development, when the embryo is composed of four cells. Only two of the four cells express PRDM14. The researchers then introduced artificially higher levels of PRDM14 in two of the cells and followed their fate. The results showed that those expressing PRDM14 at an early stage became the future embryonic stem cells. They propose that the modifications at the chromatin triggered by PRDM14 could be mediated through its interaction with another protein that also modifies chromatin: CARM1.

 

This study establishes that the fate of future embryonic stem cells may be determined very early in development, when the embryo is composed of only four cells. Through the epigenetic changes caused in the chromatin, CARM1 and PRDM14 appear to play a crucial role in the initial establishment of this cell line. These results open perspectives in the field of cellular therapy. By knowing the molecular components that triggers the formation of embryonic stem cell, researchers could develop new tools to reprogram cells into stem cells able to recreate any type of tissue in a more efficient fashion.

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