Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment

It is believed that a primitive cell type that maintains the mesenchymal compartment exists in the bone marrow. However, this putative mesenchymal stem/progenitor cell is yet to be identified and isolated. We are reporting the identification, isolation, and detailed characterization of the most primitive mesenchymal progenitor cells in the adult murine bone marrow, based on the expression of stage-specific embryonic antigen-1 (SSEA-1). This primitive subset can be identified in mesenchymal cell cultures and also directly in the bone marrow, thus ascertaining for the first time their existence in an adult organism. Characterization of SSEA-1(+) mesenchymal cells revealed that upon purification these cells gave rise to SSEA-1(-) mesenchymal cells, whereas the reverse could not be observed. Also, these SSEA-1(+) cells have a much higher capacity to differentiate than their negative counterparts, not only to several mesenchymal cell types but also to unconventional cell types such as astrocyte-, endothelial-, and hepatocyte-like cells in vitro. Most importantly, a single-cell-derived population was capable of differentiating abundantly into different mesenchymal cell types in vivo. Altogether we are proposing a hierarchical organization of the mesenchymal compartment, placing SSEA-1(+) cells at the apex of this hierarchy.