How to make a red blood cell – and fast

Understanding how normal blood cells are made in the body can help us understand what goes wrong in blood-related diseases such as anaemia (a lack of red blood cells) and leukaemia (cancer of the blood). Guest writer Dr. Gemma Swiers describes recent research by Claus Nerlov’s group in the WIMM that has made an exciting breakthrough in understanding how the body produces red blood cells – especially when they are needed most.

Red blood cells are one of the smallest and most common types of cell in your body, whose function is to feed your tissues and organs with oxygen.  Despite their abundance, however, these are not the only type of cell in your blood.  There are also white blood cells (myeloid and lymphoid cells) that fight infections, and platelets that help the blood to clot. Together, these cells make up your blood system.

But where do they come from? Fascinatingly, all of these different blood cell types can be made from a single, highly specialised type of cell. This cell is found in the spongy core in the middle of your bones called the bone marrow, and is known as a blood (hematopoietic) stem cell. Whilst much interest in these rare cells has been sparked by the success of bone marrow transplants in the treatment of leukaemia, there is still much that scientists do not understand about this fascinating process. However, a recent study by Claus Nerlov’s group at the WIMM adds an important piece to this incredibly complex puzzle.

Several labs in the WIMM focus on trying to understand precisely how this process works: how these incredibly versatile blood stem cells are able to make all the different types of highly specialised blood cells that we have in our bodies. Whilst much interest in this field of research has been sparked by the success of bone marrow transplants in the treatment of leukaemia, there is still much that scientists do not understand about this fascinating process. However, a recent study by Claus Nerlov’s group at the WIMM adds an important piece to this incredibly complex puzzle.

Specialised proteins known as cytokines help the stem cells decide which intermediate cell types are made, depending on the types of blood cells the body needs at that time. A recent paper from the Nerlov group has focused on a cytokine called erythropoietin. Known as Epo for short, this cytokine stimulates red blood cell production, and is therefore commonly used to treat blood conditions like anaemia where patients have fewer red blood cells than normal. Because of its ability to increase red blood cell production and provide more oxygen, Epo has also become famous as a performance-enhancing drug in the sporting world, particularly in cycling and other endurance events.

Scientists have known for some time that blood stem cells form intermediate cell types called progenitors, which are halfway between a stem cell and a fully formed blood cell. As these cells divide they become increasingly specialised, until they form a single specific cell type. For example: one type of intermediate progenitor cell can make lymphoid and myeloid cells but not red blood cells or platelets; whereas others can only make myeloid cells; and another can only make red blood cells and platelets. This process is known as lineage commitment.

The research by scientists in the Nerlov lab demonstrates for the first time that in addition to stimulating committed red blood cell progenitors to produce fully formed red blood cells, Epo can also target the blood stem cells in the bone marrow, preventing these multi-tasking stem cells from making myeloid or lymphoid progenitors. Epo therefore effectively creates a differentiation superhighway where the blood stem cells are encouraged to churn out red blood cells, and red blood cells alone.

This exciting work adds a new dimension to scientists’ understanding of how cytokines work. The implications of these findings are far reaching; this information could not only lead to new tests to help detect performance-enhancing drugs in sport, but most importantly it may help to identify, develop and refine treatments for diseases that affect red blood cell production.

Post edited by Bryony Graham and Claus Nerlov.