Currently, text books say the life-long supply of the billions of blood cells in our veins is driven by a small pool of multipotent blood stem cells. Much of the evidence to support this comes from studies of what happens following a bone marrow transplant. However, a new study by researchers developing a stem cell barcoding tool suggests this is the exception.
Writing about their work in Nature, the Harvard scientists describe how, using a new tool that generates a unique barcode of cellular DNA, they identified differences in origin between individual blood cells in mice to “reveal unprecedented features” of how blood cells are formed.
They conclude that it is not blood stem cells but a large number of long-lived descendants of stem cells called progenitor cells that are responsible for the normal daily supply of blood cells during most of adulthood.
Stem cells do not drive the production of the daily supply but likely act as reserves, they suggest.
The finding suggests that progenitor cells could potentially be just as valuable as blood stem cells for treatments that regenerate blood cells.
Senior author Dr. Fernando Camargo, of the Harvard Stem Cell Institute, says:
“I think that not only for the blood field, this can change the way people look at stem cell and progenitor relationships. The feedback that we have received from other experts in the field has been fantastic. This can truly be a groundbreaking technology.”
Stem cells are cells that have the potential to develop into a large range of specialized cells – they are called pluripotent or multipotent cells. Progenitor cells, which come from stem cells, are a stage further down the line; they have the potential to develop into a smaller range and so their fate is already partly pre-determined.
Using their new tool, the team generated a unique barcode in the DNA of all blood stem cells and their progenitor cells in a mouse.
When a tagged cell divides, its descendants carry the same barcode. Using this inventory tracking system, the researchers could see which stem cells and progenitor cells were being used to make blood and how long they lived, and find out where individual blood cells came from.
First author Dr. Jianlong Sun, a postdoctoral fellow in Dr. Camargo’s lab, says:
“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. One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.”
Previously, scientists have tried to tag blood cells using viruses, but this requires the cells to be removed from the body, infected and re-transplanted.
The system that Dr. Camargo and colleagues took 7 years to develop uses mobile genetic elements called transposons to label blood cells inside the body. The team now plans to use their tool to explore other uses.
“We are also tremendously excited to use this tool to barcode and track descendants of different stem cells or progenitor cells for a range of conditions,” explains Dr. Sun, “from aging, to the normal immune response.”
The researchers believe the new technology will help answer basic questions about cell populations in solid tissue. These questions include how to trace the precise origins of migrating cancer cells, such as where they broke off from in a tumor.
Funds for the study came from the National Institutes of Health (NIH) and the Harvard Stem Cell Institute.
In August 2014, Medical News Today learned about a stem cell breakthrough for “Cinderella cells.” Scientists managed to grow NMP cells – a group of cells that has been overlooked for many years – in the lab, a result that will allow researchers to understand more about embryonic development.