Research focus of the Gutjahr group
Identification and modification of intracellular signaling pathways in healthy and pathological erythrocyte formation
Red blood cells, so-called erythrocytes, are essential for life because their main task is to supply the entire organism with oxygen. Erythrocytes make up the main component of our blood. In an adult, up to 200 billion red blood cells are produced in the bone marrow every day. If this production is disturbed or if a person loses large amounts of blood through injuries, blood transfusions is necessary. Despite years of research in blood formation, the so-called erythropoiesis, we are still dependent on voluntary blood donations to cover the worldwide need of 80 million blood units per year in transfusion medicine. Healthcare systems worldwide are faced with a shortage of blood products. Therefore, it is of great importance to decipher the molecular mechanisms of erythroid differentiation from a stem cell to a red blood cell.
Figure 1: The individual steps of erythroid differentiation in the bone marrow are characterized by the loss of the transferrin receptor (CD71, yellow), the increased production of erythroid-specific surface molecules such as glycophorin A (GPA, magenta) and the shrinkage and ejection of the cell nucleus (purple).
In our previous research, we were able to show that progenitor cells of the erythrocytes, so-called erythroblasts, express chemokine receptors, which were previously mainly associated with the migration of immune cells. Our research aims to understand the function of these chemokine receptors on erythroblasts, which is fundamentally different from that of immune cells as they do not induce migration of erythroid cells.
Figure 2: The smallest functional unit of erythropoiesis in the bone marrow is the so-called erythroblastic island. A central macrophage (red) is surrounded by erythroblasts (green) in order to phagocytose the cell nucleus (blue) after it has been ejected.
There are various diseases that are characterized by defective erythropoiesis. On the one hand myeloproliferative diseases such as polycythemia vera or erythroleukemia, on the other hand diseases characterized by defective erythropoiesis, which leads to anemia and stress erythropoiesis. By identifying the erythroid-specific signaling molecules and intracellular transportation of chemokine receptors that determine the signaling pathways of the chemokine receptors in erythroid cells, we want to contribute to more efficient and drug-controlled blood production in the future.
