Led by Nancy Speck, PhD, Professor of Cell and Developmental Biology at the University of Pennsylvania School of Medicine, the researchers have identified the location and developmental timeline in which a majority of bone marrow stem cells form in the mouse embryo, reports Nature.
Speck said that the results underline critical steps in the origin of hematopoietic (or blood) stem cells (HSCs), found in the bone marrow of adult mammals.
A small number of endothelial cells express Runx1 (blue cells) at the time of development, signalling the production of grapelike clusters of hematopoietic (or blood) stem cells along the interior walls of several major blood vessels in the mouse embryo.
This cluster of endothelial cells is in the lumen of the vitelline artery, which passes from the yolk sac to the primitive aorta in young vertebrate embryos.
As HSCs generate all of the blood cell types of the body, discovery of their origin may help researchers to better manipulate embryonic stem cells to generate new blood cells for therapy.
"The ultimate goal for stem cell therapies is to take embryonic stem cells and push them down a particular lineage to replace diseased or dead cells in human adults or children," said Speck.
For instance, in theory embryonic stem cells could be tweaked in a lab to provide a patient with bone marrow failure a fresh supply of compatible HSCs.
However, Speck said that till date scientists have failed to coax embryonic stem cells to become HSCs without significant genetic manipulations that are too risky for clinical therapies.
Previous studies indicated HSCs originated from a small population of cells lining the blood vessels, called endothelial cells, but how they transitioned to blood stem cells during early development was still unclear.
Also, a study highlighted the role of a protein called Runx1, which is known to be critical in the formation of blood cells, in this important transition.
In the new study, the researchers inactivated the gene that codes for the protein Runx1 in the endothelial cells of mouse embryos.
They halted HSC production by selectively blocking the ability of endothelial cells to express Runx1 during embryo development, demonstrating that Runx1 is vital to the endothelial cell to HSC transition.
Then, they shut off Runx1 expression in mouse embryos at day 11.5 of gestation, which is a time when most newly born HSCs have detached from the vessel wall and migrated to the foetal liver.
The researchers found that blocking Runx1 expression had no effect on HSC formation, suggesting while Runx1 is required for the transition from endothelium to HSCs, the process is complete by the end of the 11th day of gestation.
The researchers also showed that at least 95 percent of all adult HSCs (and therefore almost all adult blood) originate in the endothelium, during this short window of time during development.
Speck said that understanding the location and developmental timeline of the origin of blood stem cells will help guide future efforts to coax embryonic stem cells to produce mature blood cells.
The study is appearing online in the journal Nature. (ANI)