A barcoding and tracking system for tissue stem cells has revealed previously unrecognized features of normal blood production: Surprisingly, the billions of blood cells produced in the body each day are not made by blood stem cells, but by their less pluripotent descendants – progenitor cells.
Based on these findings, published in Nature, the, the researchers hypothesize that blood comes from stable populations of different long-lived progenitor cells that are responsible for giving rise to specific blood cell types. Blood stem cells, meanwhile, likely act as reserves. This means that these progenitor cells could potentially be just as valuable as blood stem cells for blood regeneration therapies.
This look into the origins of blood cells was made possible by the new “barcoding” tool developed at the Boston Children’s Hospital. The tool generates a unique barcode in the DNA of all blood stem cells and their progenitor cells in a mouse. When a tagged cell divides, all of its descendant cells possess the same barcode. This biologic inventory system makes it possible to determine the number and lifetime of stem cells/progenitors being used to make blood, and to answer fundamental questions about where individual blood cells come from.
“There’s never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation,” study author Jianlong Sun, PhD, of Boston Children’s Hospital, said. “We can now revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.”
The researchers are now planning to explore many more applications for their barcode tool, such as tumor progression and identifying the precise origins of circulating cancer cells that have broken off from a tumor.
- Sun J, Ramos A, Chapman B, et al. Clonal dynamics of native haematopoiesis. Nature. 2014;514:322-7.