The intriguing very small embryonic-like stem Sca-1(+)/Lin(-)/CD45(-) cells (VSELs) in adult murine bone marrow that express several epiblast/germ line and pluripotent stem cell markers (e.g., Oct-4 and SSEA-4) has been driven to differentiate along the hemato/lymphopoietic lineage.
For this purpose purified from bone marrow, VSELs were primed/cocultured over OP9 stroma cell line and subsequently tested in vitro and in vivo assays for their hematopoietic potential.
In parallel, cells derived from VSELs were evaluated for expression of hematopoietic genes and surface markers.
Such study have shown that although freshly isolated VSELs do not exhibit in vitro and in vivo hematopoietic potential, they may, after coculture over OP9 stromal cells, differentiate along the hematopoietic lineage in a similar way as embryonic stem cells or inducible pluripotent stem cells.
"OP9-primed," VSEL-derived cells acquired expression of several hemato/lymphopoiesis-specific genes and markers, gave rise to hematopoietic colonies in vitro, and protected lethally irradiated mice in both primary and secondary transplant models on transplantation.
The most intriguing thing was that, compared to hematopoietic stem/progenitor cells, VSELs are highly resistant to total body irradiation this fact is very important due to the application of radiotherapy to the patients, as cancer cells can posses such features either.
Nevertheless based on these observations, it can be postulated that VSELs are the most primitive murine bone marrow-residing population of stem cells that have the potential to become specified into the hematopoietic lineage and may share some of the characteristics of long-term repopulating HSCs.