Demonstration That Thylo Subsets of Mouse Bone Marrow That Express High Levels of Lineage Markers Are Not Significant Hematopoietic Progenitors

Abstract

We have been unable to reproduce experiments suggesting the existence of three lineage-restricted progenitor populations from mouse bone marrow. Thy1.1loMac-1+B220+ cells were reported to give rise to greatly expanded numbers of myeloid and lymphoid cells, while Thy1.1loMac-1+B220- and Thy1.1loMac-1-B220+ cells were reported to be highly proliferative myeloid and B-lineage-restricted progenitors, respectively. Both Mac-1+ cell types appear to be much less frequent than previously reported, and we observed no activity consistent with their characterization as committed progenitors of expanded numbers of cells. The original identification of these populations may have resulted from a failure to distinguish bonafide signals from autofluorescent background and nonspecific staining. The progenitor activities originally associated with these populations may have been due to hematopoietic stem cell contamination. This study shows that low levels of Mac-1 are expressed on cells with multipotent progenitor activity. Thy1.1loB220+Mac-1- cells can be purified from bone marrow, but in these experiments they do not give rise to detectable levels of progeny on injection into lethally irradiated mice. Thy1.1loB220+Mac-1- cells appear to be pro-B cells without significant proliferation potential in vivo. The finding that the described populations do not have the reported progenitor activities leaves the pathways of stem cell differentiation open to further study.