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This review summarizes information regarding the rare population of very small embryoniclike stem cells VSELs that has been identified in adult tissues, emphasizing both their unique morphological features and potential biological significance. We focus on their pluripotent nature and expression of markers characteristic for embryonic stem cells ESCs, epiblast EPSCs, and primordial germ cells PGCs. Furthermore, we will discuss their rank in the developmental hierarchy of the SC compartment as well as their relationship to other bone marrowderived, primitive, nonhematopoietic SCs including: i endothelial progenitor cells EPCs; ii mesenchymal MSCs; iii multipotent adult progenitor cells MAPCs; iv marrowisolated adult multilineage inducible MIAMIs cells; v multipotent adult MASCs; and vi OmniCytes. We will also present different populations of very “small SCs” that have been recently described in the literature e.g., sporelike cells and Lin−ALDHhighlongterm repopulating hematopoietic SCs. © 2008 International Society for Advancement of Cytometry

Recently, we purified a population of CXCR4Oct4SSEA1Sca1Lin−CD45−very small embryoniclike stem cells VSELs from adult murine bone marrow BM. After using flow cytometry, ImageStream analysis, confocal microscopy, and real time RTPCR, we report that similar cells could be also identified and isolated from several organs in adult mice. The highest total numbers of Oct4VSELs were found in the brain, kidneys, muscles, pancreas, and BM. These observations support our hypothesis that a population of very primitive cells expressing germ lineepiblast markers Oct4, SSEA1 is deposited early during embryogenesis in various organs and survives into adulthood. Further studies are needed to determine whether these cells, after being isolated from various adult human organs similarly to their murine BMderived counterparts, are endowed with pluripotent stem cell properties. © 2008 International Society for Advancement of Cytometry