What prevents embryonic stem cells from differentiating?
Revealing the secrets of stem cells
LifeSciencesToday based on Carnegie Institution for Science: Solving Stem Cell MysteriesThe ability of embryonic stem cells to differentiate into different types of cells with different functions is regulated and maintained by a complex sequence of chemical interactions that remain poorly understood today.
A deeper understanding of the differentiation process could play an important role in the development of stem cell-based therapies.
A group of scientists from the Carnegie Institution focused their attention on the process by which stem cells maintain their inherent undifferentiated state. The results of their study are published in the journal Cell (Regulation of Pluripotency and Self-Renewal of ESCs through Epigenetic-Threshold Modulation and mRNA Pruning).
Embryonic stem cells are characterized by a process of self-renewal, during which they divide without differentiating into other cell types. This process depends on three protein networks that control both self-renewal and final differentiation. But the relationship of these three networks remained a mystery.
In experiments on mouse embryonic stem cells, American scientists have uncovered a mechanism that integrates all three networks involved in the process of self-renewal of stem cells into a single functional whole, and found the most important missing link in this process.
The key is the Utf1 protein. He plays three important roles. Firstly, it provides a balance between the activation and deactivation of genes necessary to direct the cell towards differentiation. At the same time, it affects the matrix RNAs – the transcription products of activated genes – by placing labels that lead to degradation of mRNAs, and thus preventing them from continuing to perform their function. Finally, the Utf1 protein blocks genetic feedback, which usually suppresses cell proliferation, and thereby preserves the proliferation character characteristic of embryonic stem cells.
Utf1 protein is one of the components of bivalent chromatin of embryonic stem cells. It sets a limit to the transcriptional activity of bivalent genes such as Arf, contributing to the cytoplasmic degradation of their matrix RNAs by decapping them. In addition, it binds key pluripotency factors to Myc and PRC2 networks, promoting pluripotency and proliferation of embryonic stem cells. (Fig. cell.com )
The non–catalytic subunit of the mRNA decapitation complex (green) is present both in the cytoplasm and in the nucleus (in the image on the right, colocalized with chromatin - blue) of embryonic stem cells. (Photo: Carnegie Institution)
"We are slowly but surely getting closer to understanding the physiology of embryonic stem cells," says study leader Yixian Zheng, PhD. "It is very important to continue basic research related to the functions of these cells."
In addition to scientists from the Carnegie Institute, experts from The Scripps Research Institute and the National Institutes of Health contributed to the study.
Portal "Eternal youth" http://vechnayamolodost.ru02.11.2012