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Red blood cells, Stem cells

The stem cell that keeps you topped up with blood

Our blood is made up of a huge number of different cell types responsible for oxygen distribution, blood clotting and fighting infection. So, have you ever wondered where all these different blood cells come from? Believe it or not it is down to one type of cell, called hematopoietic stem cells, which can give rise to which ever blood cell type the body needs. In this blog post Christina Rode discusses and visually explains where these cells come from, what they do and why they are so important.

In adults, hematopoietic stem cells (HSCs) are the cells that reside in the bone marrow that are responsible for constantly replenishing all the blood cells in your body. But while research into these cells has been done for over half a century, scientists are only just beginning to recreate the right conditions to generate these stem cells outside the body. Still many questions and caveats remain. What is fascinating is that a tiny embryo intrinsically knows how to generate these cells. So, it is this embryonic wisdom scientists are making use of to study HSCs.

To try and understand how the embryo makes these HSCs, scientists study mouse embryos (among other organisms). At the early stage of the mouse pregnancy (day six of a 20 day pregnancy), the embryo consists of only three different cell types, called germ layers. One of them, the mesoderm, takes centre-stage in HSCs development, as this is the embryonic origin of the entire blood system.

As the embryo develops, the mesoderm starts to segment itself, with each portion maturing into a more specialised mesoderm cell type. Some of these specialised mesoderm cells mature into cells that give rise to the heart or muscle, while others mature into the first blood-related cell types.

The first two stages of blood development happen in the embryonic yolk sac and rapidly generate the very first blood progenitors. These progenitors immediately precede mature cells of different blood lineages and initially support the early development of the embryo. They are distributed from the yolk sac to the embryo via the vascular system as soon as the heart starts beating. In fact, while the first waves of blood development are underway, the vascular system of the embryo is assembled. Interestingly, blood cell development and vessel development are intricately linked.

The most important stage of blood development is the last stage, when the first HSCs are generated around mid-pregnancy. It was at this point that we can see the close relationship between blood and endothelial cells in the main blood vessel (aorta) of the mouse embryo. When scientists created a time-lapse video of the aorta, they observed something remarkable: a specialised portion of endothelial cells, called hemogenic endothelial cells, started changing their shape from an elongated cell to a rounder cell shape. When scientists looked at these round cells in more detail, they found they were actually blood progenitor cells. You can see a computer-generated animation of how this endothelial-to-hematopoietic transition happens below. I have made this scientific animation as part of a workshop with Monica Zoppe (http://www.scivis.it/) using the Blender software.

Unlike the blood progenitor cells in the yolk sac, some of these aortic blood progenitor cells actually had the ability to mature into true HSCs, and were therefore named pre-HSCs. We now know that after detaching from the aortic wall these pre-HSCs are carried with the blood flow to the liver. The liver then provides the perfect environment to allow the final maturation of these pre-HSCs to become fully functional HSCs. Just before birth, these HSCs make their last move to the bone marrow, where they stay for the rest an organism’s life making all types of blood cells.

What makes HSCs so good at their job is their ability to give rise to different blood cells depending on what the body needs. They can either make an identical version of themselves (self-renewal, ‘safe for later’) if everything is in balance or they can continue to mature into a specific blood cell (differentiation, ‘need now!’) if more blood cell numbers are needed or a blood cell type needs replacing . Both of these processes are unique to a HSC and are necessary to maintain a healthy blood system throughout a person’s life.

When the controlling factors that regulate self-renewal or differentiation of HSCs stop working, the system is thrown off-balance. If self-renewal goes into over-drive, blood-related cancers can develop. And if differentiation is faulty, it can lead to the overproduction of one, but under-production of another, blood cell type, which can cause anaemia.

So, with the many complexities of HSCs from their generation to their ever-changing job in the body, it is understandable why these cells are so hard to generate and maintain outside of the body.  But as scientists continue to study HSCs, their role in health and disease, and optimise the conditions required to grow them in the laboratory, we can better understand them and harness their abilities for future treatments of blood-related diseases.

This blog was edited by Lauren Howsen and Emma O’Brien.

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