Genes that make stem cells
The increased interest in the problem of stem cells is due to the possibilities of their use for the treatment of diseases. However, despite the obvious progress in this field and the successful therapeutic application in the experiment, research on stem cell genetics is still far from complete. The identification of genes that determine the properties of stem cells will not only accurately identify these types of cells, but also open up new opportunities to control them during cultivation and therapeutic use.
The special characteristics of stem cells are determined not by one gene, but by a whole set of them. The possibility of identifying these genes is directly related to the development of the method of cultivation of embryonic stem cells (ESCs) in vitro, as well as the possibility of using modern methods of molecular biology. In the presence of leukemia inhibition factor LIF (leukemia inhibitory factor) in the culture medium ESCs are maintained in vitro in an undifferentiated state. If LIF is removed from the medium, then ESCs begin to differentiate and form complex structures called embryoid bodies and consist of cells of various types that are precursors of nerve, muscle, endothelial and hematopoietic cells.
As a result of joint research by Geron Corporation and Celera Genomics, cDNA libraries of undifferentiated ESCs and three populations of partially differentiated cells were created. [cDNA is obtained by synthesis of a complementary DNA molecule based on an mRNA molecule using the reverse transcriptase enzyme.] When analyzing data on sequencing of nucleotide sequences and gene expression, more than 600 genes were identified, the inclusion or deactivation of which distinguishes undifferentiated cells and a picture of the molecular pathways along which these cells differentiate is compiled.
Currently, scientists distinguish stem cells by their behavior in culture and by chemical markers on the cell surface. However, the genes responsible for the manifestation of these features remain unknown in most cases. Nevertheless, the conducted research allowed us to identify two groups of genes that give stem cells their remarkable properties. On the one hand, these are genes that function in various types of stem cells, 283 such genes have been identified. On the other hand, the properties of stem cells manifest themselves in a certain microenvironment known as the stem cell niche. When studying these cells, which surround, nourish and support stem cells in an undifferentiated state, about 4,000 genes were discovered. At the same time, these genes were active in the cells of the microenvironment, not inactive in all other cells.
In the study of embryonic stem cells of drosophila ovaries, a system of signals between stem cells and specialized cells of the "niche" was determined. This signal system determines the self-renewal of stem cells and the direction of their differentiation. Regulatory genes in niche cells give instructions to stem cell genes that determine the further path of their development. Both genes produce proteins that act as switches that start or stop the division of stem cells. It was found that the interaction between niche cells and stem cells that determines their fate is mediated by three different genes - piwi, pumilio (pum) and bam (bag of marbles). It is shown that for successful self-renewal of embryonic stem cells, the piwi and pum genes must be activated, whereas the bam gene is necessary for differentiation. Further studies have shown that the piwi gene is part of a group of genes involved in the development of stem cells of various organisms belonging to both the animal and plant kingdoms. There are genes similar to pum and bam in mammals, including humans. Based on these findings, the authors suggest that the piwi niche cell gene ensures the division of embryonic stem cells and maintains them in an undifferentiated state by suppressing the expression of the bam gene.
The database of genes that determine the properties of stem cells is constantly updated. A complete catalog of stem cell genes can improve the process of their identification, as well as clarify the mechanisms of functioning of these cells, which will facilitate the production of differentiated cells necessary for therapeutic use, as well as provide new opportunities for drug development. The importance of these genes is great, as they provide the body with the ability to preserve itself and regenerate tissues.