You wouldn’t know it, but your blood is very busy indeed, turning over a staggering 300 billion cells each day. Since the 60s, scientists have thought they had a pretty good idea of how blood is made, and textbooks have changed little since then. But a new discovery turns this long-held dogma on its head, suggesting a system believed to be in place might not even exist. Not only that, but what goes on in the early days of development seems to be different in adults, which hadn’t been proposed before.
However, this work is about far more than proving textbooks “wrong.” As lead researcher John Dick from the University of Toronto explained: “Our discovery means we will be able to understand far better a wide variety of human blood disorders and diseases – from anemia, where there are not enough blood cells, to leukemia, where there are too many blood cells. Think of it as moving from the old world of black-and-white television into the new world of high definition.” His team's work has been published in Science.
In the classical view of blood formation - or hematopoiesis - a kind of hierarchy of “potency” exists, which refers to a cell’s ability to give rise to, or differentiate into, different types of cells. If you’ve read anything about stem cells, you might be familiar with the term; pluripotent stem cells are those that can turn into virtually any cell of the body and are thus desirable for regenerative medicine and personalized cell therapies.
In the blood, the hierarchy was believed to start with so-called multipotent and hematopoietic stem cells (HSCs) that are small in number but capable of self-renewal, some of which also have long lifespans. Further on down the line, through “oligopotent” and “unipotent” intermediate stages, cells progressively lose their ability to differentiate but become more numerous and short-lived, ultimately differentiating into more than 10 different types of blood cells. Imagine the whole thing like a tree, with the multipotent cells representing the trunk at the bottom, gradually branching out into the different cell types.
But it turns out that a rather different route of development might actually be occurring. To scrutinize the process, scientists developed a cell-sorting scheme and examined the lineages of close to 3,000 human cells with 33 different origins, obtained from individuals of varying ages. While they found evidence for large populations of distinct progenitor cells early on in development, in adults different types of blood cells were found to form from stem cells much earlier than believed, only going through a few precursor stages. Check out the model below to help you visualize.
Image credit: Notta et al., Science 2015.
In fact, in adults only two classes of progenitor cells were found to dominate the bone marrow: multipotent and unipotent, representing what they have defined as a “two-tier” hierarchy. The existence of differing systems between fetal stages and adulthood goes against ideas that scientists have held for years, and will hopefully lead to a better understanding of diseases of the blood.