October 8, 2014

Image Caption: New genetic barcoding technology allows scientists to identify differences in origin between individual blood cells. Credit: Camargo Lab

Provided by Joseph Caputo, Harvard University

New technology that tracks the origin of blood cells challenges scientific dogma

A 7-year-project to develop a barcoding and tracking system for tissue stem cells has revealed previously unrecognized features of normal blood production: New data from Harvard Stem Cell Institute scientists at Boston Childrens Hospital suggests, surprisingly, that the billions of blood cells that we produce each day are made not by blood stem cells, but rather their less pluripotent descendants, called progenitor cells. 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, while blood stem cells likely act as essential reserves.

The work, supported by a National Institutes of Health Directors New Innovator Award and published in Nature, suggests that progenitor cells could potentially be just as valuable as blood stem cells for blood regeneration therapies.

This new research challenges what textbooks have long read: That blood stem cells maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplantsa fact that still remains true. But because of a lack of tools to study how blood forms in a normal context, nobody had been able to track the origin of blood cells without doing a transplant.

Boston Childrens Hospital scientist Fernando Camargo, PhD, and his postdoctoral fellow Jianlong Sun, PhD, addressed this problem with a tool that 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 biological inventory system makes it possible to determine the number of stem cells/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.

Theres 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, Sun said. 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.

People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues, said Camargo, who is a member of Childrens Stem Cell Program and an associate professor in Harvard Universitys Department of Stem Cell and Regenerative Biology. I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons.

Read more:
Scientists Develop Barcoding Tool For Stem Cells