Research Perspective Volume 2, Issue 11 pp 875—883

Figure 2. Reprogramming of genomic imprinting controls the pluripotentiality and quiescence of VSELs. During development, PGCs and VSELs undergo similar epigenetic reprogramming of genomic imprinted genes (black bar above the indicated cells); however, they also retain expression of some pluripotent genes (e.g., Oct4) through maintaining the corresponding promoter's DNA demethylation (red bar below the indicated cells). Intriguingly, VSELs undergo the parent-of-origin-specific reprogramming of somatic imprints, resulting in upregulated maternally expressed/proliferation-repressing imprinted genes (H19, p57^KIP2, and Igf2R, up-red arrow) and down-regulated paternally expressed/proliferation-promoting genes (Igf2 and RasGRF1, blue-down arrow). In particular, the erasure of genomic imprints in these cells is responsible for preventing them from aberrant teratoma formation, but at the same time restrains their pluripotentiality. In contrast, differentiated somatic cells lose their pluripotency by turning off the transcription of pluripotent genes through stable DNA methylation of their promoters (e.g., Oct4). However, they retain the somatic pattern of the genomic imprint. Thus, somatic cells may be dedifferentiated to PSCs by expression of pluripotent genes (blue box: iPSC protocol). In contrast, PGCs that express pluripotential genes, but erase the somatic imprint, may become pluripotent embryonic germ cells (EGCs) by proper remethylation of some of the erased imprinted genes (green box: EGC protocol). We hypothesize that similar modulation of parent-of-origin-specific reprogramming of somatic imprints in VSELs that enforces their quiescent state in tissues may “unleash” their pluripotentiality and reverse them to a fully pluripotent state (dark blue box: VSEL protocol). M.M.: maternally methylated loci; P.M.: paternally methylated loci.