CellRes analyzes essential elements for stem cell differentiation
Researchers from the Institute of Advanced Translational Medicine of Tongji University and Tsinghua University found that the process of embryonic stem cell differentiation requires a histone modification that plays an important role in the regulation of gene transcription, which will help the further research of embryonic stem cell differentiation. Related content is delivered to Cell Research magazine in the form of a letter.
Leading this research is Professor Sun Fanglin, Dean of the School of Life Science and Technology, Tongji University. He returned to China in 2006 and was selected into the Tsinghua University "Hundred Talents Program." Chief scientist of the "973" project of the Ministry of Science and Technology.
Epigenetic regulation, especially the advanced organization of chromosomes in the nucleus, is currently a frontier and hot issue in stem cell research. Pluripotent stem cells, including embryonic stem cells and induced stem cells, can use a complex network of genetics and epigenetics to maintain a precise balance between self-renewal and multi-directional differentiation.
In epigenetic regulation, histone modification occupies a large part, and its modification methods include acetylation, phosphorylation, glycosylation, and ubiquitination, and the monoubiquitination of histone H2B lysine 120 (Histone H2B Lysine 120 monoubiquitination (H2BK120ub) plays a key role in the regulation of gene transcription in many species and in advanced ordered chromatin organization.
Previous studies have shown that H2BK120 and H2BK123 are relatively conserved sites for ubiquitination, and are closely related to highly expressed active genes in human cells. But the role it plays in embryonic stem cells is unclear. In this article, the researchers used ChIP and other methods to find that the monoubiquitination of histone H2B lysine 120 is essential for embryonic stem cell differentiation.
This not only proves the effect of epigenetic regulation on stem cells, but also further explores the molecular mechanism of epigenetic regulation of "stemness" of pluripotent stem cells.
As early as 2006, researchers at the Burnham Institute of Medical Research discovered that the chemical modification of human embryonic stem cell DNA has a characteristic and predictable pattern. This model distinguishes human embryonic stem cells from normal adult cells and cell lines (including cancer cells).
Embryonic stem cells are derived from embryos that undergo intense cell activity, and these acquisitions also include DNA methylation processes. The methylation and demethylation of specific DNA sequences in the genome have a profound effect on cell behavior and differentiation.
Later, scientists from Cambridge University and other places discovered that mouse pluripotent stem cells have heterogeneous differentiation potential. This mechanism is controlled by epigenetic mechanism. The expression of stella in embryonic stem cells is different. Stella is a biological marker of pluripotent cells and germ cells. The study found that stella-positive embryonic stem cells developed into endoderm cell clusters, and stella-negative embryonic stem cells developed into ectoderm cell clusters. This situation (stella positive or negative) is interchangeable, which also confirms that the embryonic stem cells are indeed very plastic. These embryonic stem cells are in a metastable state and therefore have strong plasticity. When the signal released by the feeder cells changes, the stem cells that have established a stable state can also change, which will cause the biomarkers of the ectoderm cells to change. This feeder cell change comes from gustastatin A, which is an inhibitor of histone deacetylase, which can alter the repair stella marker.
These studies have gradually and deeply verified the importance of epigenetic regulation in pluripotent stem cells, and the recent development of high-throughput genome research tools has greatly promoted the research field of epigenetic regulation in pluripotent stem cells. There is evidence that some epigenetic pathways, such as modification of DNA, histones and nucleosomes, have extensive crosstalk. And some new drawing tools (drawing a map of chromosome structure and chromosome-nuclear matrix interaction) also for the first time depict the three-dimensional structure of the genome, and a framework that integrates existing apparently regulated genomic data together, which can find more More about new mechanisms of gene regulation.
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