Molecular Signature of Very Small Embryonic-like Stem Cells

Abstract

Tissue and organ rejuvenation and senescence/aging are closely related to the function of stem cells. Thus, stem cells have been considered as guardians for the homeostasis of tissue/organ throughout life span. Recently, we identified a population of pluripotent Oct4+ very small embryonic/epiblast-like stem cells (VSELs) residing in the adult murine bone marrow (BM) and human cord blood (CB). VSELs can differentiate into cells from all three germ layers in vitro culture condition and in vivo tissue regeneration animal models. VSELs express the gene-expression and epigenetic profiling, which are similar to germ-line stem cells including (i) open/active chromatin structure in Oct4 promoter, (ii) parent-of-origin-specific reprogramming of genomic imprinting, (iii) deoxyribonucleic acid (DNA) demethylation in the promoter of germ-line lineage genes, and (iv) reactivate the X chromosome (in female pluripotent stem cells, PSCs). The unique epigenetic reprogramming in VSELs suggest that they could developmentally originate from the migratory primordial germ cells (PGCs) and the proliferation of VSELs are negatively controlled by epigenetic changes of some imprinted genes that regulate insulin/insulin-like growth-factor (Ins/Igf) signaling (Igf2, H19, Igf2R, and Rasgrf1). Since the chronic exposure to Ins/Igf signaling negatively correlates with longevity, we propose that Ins/Igf signaling mediated decrease in the number of VSELs could be a novel explanation of ageing. Therefore, VSELs could play a pivotal role in maintaining the integrity of adult tissues and these cells could provide a therapeutic alternative to stem cells isolated from embryos. Therefore, the understanding the precise molecular signature of VSELs such as reprogrammed genomic imprints could increase the regenerative power of these cells.