Every day, over 100 billion new mature blood cells are generated in an adult human. This major production places high demands on the blood stem cells which must be capable both of maturing into specialised blood cells and of self-renewing and multiplying. An important element in getting blood stem cells to multiply outside the body is to understand which of the approximately 20 000 genes in the human body control their growth. Now, a study from researchers at Lund University has studied close to 15 000 of these genes alongside each other; a feat which is unprecendented. The team state that they have succeeded in identifying four key genes which, together, govern the growth and multiplication of the stem cells. The opensource study is now being published in the journal Cell Reports.
Previous studies show in a bone marrow transplant, blood stem cells are responsible for the formation of a new blood system. In order to make stem cell transplants safer and available to more patients with diseases such as leukemia or hereditary blood disorders, researchers in many parts of the world are studying how to expand and multiply blood stem cells. However, many of the fundamental mechanisms of the process are still unknown. An important step on the way is to map which of the thousands of human genes affect the regulation of stem cell growth. The current study used RNA interference, a technique in which individual genes in the stem cells are selectively neutralized, to successfully identify the genes which affect the regulation of blood stem cells.
The current study of the 15 000 genes found around 20 candidates with a strong capacity to affect the balance of growth in the blood stem cells. Results show that four of these 20 genes were physically connected through cooperation in a protein complex. Data findings show that this protein complex is crucial and has an overarching function in the growth of the blood stem cells.
Results show that the protein complex, consisting of the four genes plus one further gene, is called cohesin and forms a sort of brace which holds different parts of the DNA strand together in the cell. The lab hypothesize that this allows the cohesin complex to control access to the ‘on/off switches’ in the DNA, and to change the impulses the blood stem cells receive from various genes, thereby affecting cell division. They conclude the blood stem cell either multiplies or matures to become a specialised cell with other tasks.
The group state that clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body. The go on to add that, in addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation. The researchers note that independently of their study, other teams in the field of blood cancer have recently identified mutations in the exact same four genes identified in the current study, in patients with various forms of blood cancer.
The team surmise that the results from their study indicates that the cohesin genes are directly and crucially significant in the development of blood cancer. The go on to add that their findings entail a new understanding of how the expansion of blood stem cells is controlled. For the future, the researchers state that eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.
Source: Lund University