Penn researchers unlock molecular origin of blood ...(s was responsible for this important tra...),Health

First, the researchers inactivated the gene that codes for the protein Runx1 in the endothelial cells of mouse embryos. During development, some endothelial cells express Runx1, signaling the production of grapelike clusters of HSCs along the interior walls of several major blood vessels. Upon release from the vessel walls HSCs enter the blood circulation and travel to the fetal liver, and upon birth they relocate to the bone marrow.

By selectively blocking the ability of endothelial cells to express Runx1 during embryo development, the researchers halted HSC production, demonstrating that Runx1 is vital to the endothelial cell to HSC transition.

Next, Speck's team shut off Runx1 expression in mouse embryos at day 11.5 of gestation -- a time when most newly born HSCs have detached from the vessel wall and migrated to the fetal 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.

"This study helps illustrate a very important step in the transitional stage from embryonic stem cells to HSCs the need to move through endothelial cells as an intermediary," Speck says.

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, she says.

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