"Many of the current markers we use to purify HSCs are expressed as a gradient from high to low across the hematopoietic cell hierarchy," says Omer H. Yilmaz, co-first author and a student in the Medical School's M.D./Ph.D. program. "What's really exciting about this finding is that now we have markers that turn on and off abruptly as stem cells differentiate."
Kiel and Yilmaz used microarray analysis to measure levels of gene activity in three types of cells ?hematopoietic stem cells, multipotent progenitor cells and fully developed bone marrow cells. They selected genes that were expressed at higher levels in the HSC population, as opposed to the other two types of cells. CD150, the founding member of the SLAM family of cell surface receptors, was near the top of the list.
To see if CD150 was expressed on hematopoietic stem cells, Kiel and Yilmaz transplanted CD150+ and CD150- cells into laboratory mice whose bone marrow had been destroyed by lethal doses of radiation. Healthy bone marrow was restored in six of six mice receiving CD150+ cells, but reconstitution was successful in only one of nine mice receiving CD150- cells.
When they followed the same procedure to test another SLAM marker, CD244, the results were completely opposite. Cells with CD244 receptors on their surface membranes were unable to reconstitute bone marrow in irradiated mice for more than a few weeks, while cells without CD244 receptors were able to reconstitute indefinitely. This indicated that CD244+ cells were a marker for multipotent progenitor cells (MPPs), but not for hematopoietic stem cells.
In a third step, the team tested another SLAM marker called CD48, and found it to be expressed only on more advanced cells. It was not p
Source:University of Michigan Health System