Very small embryonic-like cells: biology and function of these potential endogenous pluripotent stem cells in adult tissues.

Very small embryonic-like cells (VSELs), found in murine bone marrow and other adult tissues, are small, non-hematopoietic cells expressing markers of pluripotent embryonic and primordial germ cells. A similar cell type in humans has begun to be characterized, though with a slightly different phenotype and surface markers. Consistent with expression of pluripotency genes, murine VSELs differentiate into cell types from three germ-layer lineages in vitro, though pluripotency has yet to be shown at the single-cell level or in vivo. VSELs appear to be quiescent under steady state conditions, apparently due to partially erased imprinting and overexpression of cell cycle inhibitory genes. In vivo, VSELs can enter the cell cycle under stress conditions, but which factors regulate quiescence versus proliferation and self-renewal versus differentiation are as yet unknown, and in vitro conditions that induce proliferation and self-renewal have yet to be defined. Future experiments are needed to address whether a VSEL niche actively regulates quiescence in vivo or quiescence is cell autonomous under steady state conditions. Insights into these mechanisms may help to address whether or not VSELs could play a role in regenerative medicine in the future.