Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment.

Our current understanding of stem cells suffers from a lack of precision, as the stem cell compartment is a broad continuum between early stages of development and adult postnatal tissues, and it is not fully understood how this transition occurs. The definition of stem cell pluripotency is adapted from embryology and excludes the possibility that some early-development stem cells with pluri- and/or multipotential differentiation potential may reside in postnatal tissues in a dormant state in which they are protected from uncontrolled proliferation and thus do not form teratomas or have the ability to complement blastocyst development. We will discuss the concept that a population of very small embryonic-like stem cells (VSELs) could be a link between early-development stages and adult stem cell compartments and reside in a quiescent state in adult tissues. The epigenetic mechanism identified that changes expression of certain genes involved in insulin/insulin-like growth factor signaling (IIS) in VSELs, on the one hand, keeps these cells quiescent in adult tissues and, on the other hand, provides a novel view of the stem cell compartment, IIS, tissue/organ rejuvenation, aging, and cancerogenesis.