Our Blood Could Be Coming From a Previously Unknown Source, Mouse Study Suggests

Even the most important and well-studied systems in our bodies may sometimes surprise us.

According to a recent research in mice, blood may have two sorts of cellular beginnings as it forms mammalian bodies.

"Historically, people have believed that most of our blood comes from a very small number of cells that eventually become blood stem cells, also known as hematopoietic stem cells,"says Fernando Camargo, a cell biologist at Harvard University and one of the researchers on the mice study.

"We were surprised to find another group of progenitor cells that do not come from stem cells. They make most of the blood in fetal life until young adulthood, and then gradually start decreasing." Embryonic multipotent progenitors are the name for these cells (eMPPs).

Hematopoietic stem cells are produced from the cells that line the arteries during early development. eMPPs were previously assumed to branch out from hematopoietic stem cells at an early stage in their development.

Sachin Patel and colleagues from Harvard University used a recently established genetic barcoding approach to follow proliferating cells and discovered that hematopoietic stem cells and eMPPs came from the same lining.

To do this, the researchers introduced pieces of easily detectable DNA sequences into a region of the mouse cell's genome that would be handed on to all of the cell's children.

This allowed scientists to track out the origins of all of their target cells, demonstrating that the eMPPs were split into cells that produced the majority of lymphoid cells (a kind of white cell) in growing mice. Many immunological blood cells, particularly white blood cells, appear to be born from these eMPP cells (B and T cells).

While hematopoietic stem cells (as seen in the image below) may also create these immune cells, they do so in a much more limited way. They are more likely to develop cells that lead to megakaryocytic blood components - cells that make the components needed for blood coagulation.

"We are following up to try to understand the consequences of mutations that lead to leukemia by looking at their effects in both blood stem cells and eMPPs in mice," adds Camargo. "We want to see if the leukemias that arise from these different cells of origin are different–lymphoid-like or myeloid-like."

Furthermore, the contribution of eMPPs to blood flow tends to diminish with time, which might explain why our immune system weakens as we age.

Patel and his colleagues also looked at how this new understanding may help with bone marrow transplants, and discovered that eMPP grafts did not stay long in mice.

"If we could add a few genes to get eMPPs to engraft long term, they could potentially be a better source for a bone marrow transplant," Camargo continues.

"They are more common in younger marrow donors than blood stem cells, and they are primed to produce lymphoid cells, which could lead to better reconstitution of the immune system and fewer infection complications after the graft."

Of course, none of this applies unless the findings in people are the same. Various mammal species have different developmental paths, and this isn't always the case.

The researchers are now looking at these blood cell moms in people in the aim of developing novel therapies for aging immune systems based on their results.