Very small embryonic-like stem cells: characterization, developmental origin, and biological significance.

Bone marrow (BM) was, for many years, primarily envisioned as the "home organ" of hematopoietic stem cells (HSC). Augmenting evidence demonstrates, however, that BM, in addition to HSC, also contains a heterogeneous population of non-HSC. Recently, our group identified in BM and other adult tissues a population of very small embryonic-like stem cells (VSELs), which express several markers characteristic for pluripotent stem cells that are characteristic for epiblast/germ line-derived stem cells. Thus, we hypothesize that VSELs are a population of epiblast-derived cells that are deposited during early gastrulation in developing tissues/organs and play an important role in turnover of tissue-specific/committed stem cells. In this context, VSELs deposited in BM can give rise to long-term repopulating HSC. VSELs could be also mobilized into peripheral blood (PB), and the number of these cells circulating in PB increases during stress and tissue/organ injuries. Finally, we envision that in pathological situations VSELs are involved in development of some malignancies (e.g., teratomas, germinal tumors).