Environmental factors participate in controlling the differentiation process of blood stem cells
Our blood system consists of a large variety of "specialist" cells, such as red blood cells, which carry oxygen, and many types of white blood cells, which provide the body with protection from infections. All of these develop in the differentiation process of the blood stem cells. How is the future and "future profession" of the stem cells determined? Israeli scientists from the Weizmann Institute of Science and the Hebrew University of Jerusalem, revealed for the first time a detailed map of gene control in the differentiation process, and learned from it new principles about the way in which the differentiation process is controlled. These findings may have far-reaching consequences for basic research and later also for the world of medicine. Among other things, they may lead to the discovery of the molecular mechanism of many diseases, including neurological disorders, anemia, leukemia and more. These findings also indicate a more significant impact than we thought of environmental factors on our health.
Blood stem cells continuously renew the blood cell supply. Unlike most of the cells in our body, these cells are able to continue dividing for the rest of our lives, and later differentiate and become an adult cell of one type or another. The differentiation process includes several stages during which several dramatic changes take place - at the end of which a mature blood cell is formed, specializing in a small number of tasks. This process requires "turning on" and "turning off" thousands of genes in a precise and regulated order. Gene activity is controlled by short control sequences (switches) within the DNA itself. The activity of the control region is carried out with the help of unique proteins, called "histones", which wrap the DNA. These proteins usually keep the control regions in the "off" state, which is designed to ensure that no unwanted activation takes place. Therefore, in order to "activate" the instructions and allow access to the relevant factors, the closing mechanisms must be "opened". The regulation of these changes is influenced by environmental factors.
Dr. Ido Amit and research student David Lara-Estiaso, from the Department of Immunology at the Weizmann Institute of Science, worked in collaboration with Prof. Nir Friedman and research student Assaf Weiner, from the Rachel Vaslim Benin School of Engineering and Computer Science and the Alexander Silverman Institute of Life Sciences at the Hebrew University of Jerusalem. Together, they mapped for the first time the activation and inhibition processes of the histone proteins in the blood cell differentiation process. The scientists have developed a new epigenetic mapping method, which makes it possible to sample a small number of cells and map the state of histones along all DNA bases. This method allowed them to map for the first time the change in the control of a blood cell system, from the stem cell to the adult cells.
their research, which is published these days in the scientific journal Science, yielded surprising results: at least half of the control sequences they discovered are opened in the intermediate stages of cell differentiation. Beyond that, most of the control sequences unique to "specialist" cells are activated long before the cells reach the stage where they are activated. This is the reason why cells in the intermediate stages are much more "flexible" in their abilities than expected. "This finding changes our understanding of the process of 'determining the fate' of blood stem cells, and suggests that it is a dynamic process that is influenced by environmental factors more than was commonly assumed in the past," says Lara-Estiaso.
Although the research focused on blood cell differentiation, the scientists believe that the rules of operation of the mechanism may also be preserved in differentiation processes in embryonic development and in other mature tissues, such as the pancreas. "This research prepares the ground for understanding the control elements of the cellular differentiation process in humans," says Weiner. Locating the DNA sequence that regulates the fate of the stem cells, and understanding the mechanism that activates it, may allow in the future the development of surgical tools necessary for the development of personalized medicine, and possibly even drugs for cellular regeneration, which can reprogram the stem cells and create every blood cell we need as spare parts.
