The developmental deposition of epiblast/germ cell-line derived cells in various organs as a hypothetical explanation of stem cell plasticity?
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The embryo develops from germ cell line (fertilized oocyte) and precursors of primordial germ cells (PGC) are the first population of stem cells that are specified in mice at the beginning of gastrulation in proximal primitive ectoderm (epiblast) ? region adjacent to the extraembryonic ectoderm. These founder cells subsequently move through the primitive streak and give rise to several extra-embryonic mesodermal lineages and to germ cells. By day 7.25 of embryonic development, a cluster of PGC is visible at the basis of allantois. Subsequently PGC migrate through the embryo proper and colonize genital ridges, where they finally differentiate into sperm and oocytes. We hypothesize that during early development epiblast/germ line-derived cells including PGC become a founder populations of pluripotent stem cells (PSC). These cells are deposited during embryogenesis in various organs and may persist in these locations into adulthood ? for example in bone marrow (BM). To support this, we recently identified in BM a population of very small embryonic-like (VSEL) stem cells that express epiblast/germ line-derived cells transcription factor Oct-4 and several other PGC markers. Similarly, cells expressing Oct-4 were also identified in several adult tissues by other investigators. Thus, pluripotent epiblast/PGC may persist beyond embryogenesis in neonatal and adult tissues. Their fate is defined by several mechanisms which regulate cell proliferation and affect status of somatic imprint on selected genes responsible for pluripotency. We hypothesize that these cells play an important role in tissue/organ regeneration and their presence in adult tissues may explain phenomenon of stem cell plasticity. In pathological situations, however they may undergo malignant transformation and give rise to tumors.
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Mariusz Z. Ratajczak, Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA