Molecular characterization of isolated from murine adult tissues very small embryonic/epiblast like stem cells (VSELs)

Abstract

Pluripotent very small embryonic/epiblast derived stem cells (VSELs) as we hypothesize are deposited at begin of gastrulation in developing tissues and play an important role as backup population of pluripotent stem cells (PSCs) for tissue committed stem cells (TCSCs). We envision that during steady state conditions these cells may be involved in tissue rejuvenation and in processes of regeneration/repair after organ injuries. Molecular analysis of adult bone marrow (BM)-derived purified VSELs revealed that they i) express pluripotent stem cells markers e.g., Oct4, Nanog, Klf-4, SSEA-1 ii) share several markers characteristic for epiblast as well as migratory primordial germ cells (PGCs), and iii) possess a unique pattern of genomic imprinting (e.g., erasure of differently methylated regions at Igf2-H19 and Rasgrf1 loci and hypermethylation at KCNQ1 and Igf2R loci). This supports that VSELs are related to epiblast-derived migrating PGC-like cells and, despite their pluripotent stem cell character, changes in the epigenetic signature of imprinted genes keep these cells quiescent in adult tissues and prevent them from teratoma formation. In contrast epigenetic changes/mutations that lead to activation of imprinted genes could potentially lead to tumor formation by these cells. Mounting evidence accumulates that perturbation of expression of imprinted genes is a common phenomenon observed in developing tumors.

Expression Profile of the Stem Cell Markers in Human Hertwig’s Epithelial Root Sheath/Epithelial Rests of Malassez Cells

“…The expression of these genes suggests that HERS/ERM cells might contain more primitive stem cell characteristics. Recently, the possibility that adult stem cells (ASCs) may contain populations of cells with varying degrees of stemness has been suggested (Shin et al, 2010;Stripp, 2008;Verstappen et al, 2009). The hierarchi-cal organization of stem cells was described for various organs and tissues including the breast, intestine, limbus, lung, skin, and intestine.…”

Retraction: Detection, Characterization, and Spontaneous Differentiation In Vitro of Very Small Embryonic-Like Putative Stem Cells in Adult Mammalian Ovary

“…S1) and this may possibly reflect presence of abundant euchromatin in them, since DAPI is understood to preferentially stain heterochromatin [27,28]. Similarly, the flow sorted very small embryonic-like stem cells (VSELs) isolated from various adult tissues, always stain much lighter with DAPI as compared to hematopoietic stem cells during the gating experiments reported by Ratajczak et al [29][30][31], personal communication with Dr Ratajczak's group]. Pluripotent markers also showed differential staining pattern in the 2 populations of PSCs.…”

Novel view of the adult stem cell compartment – of germline and parental imprinting

“…We found at least three different types of libraries generated from single, sorted VSELs, and some of these libraries exhibited a strong epiblast-or PGC-like gene expression pattern. In support of such a connection, we observed that murine BM-derived VSELs express several genes that are characteristic of epiblast SCs (Gbx2, Fgf5, and Nodal) and, more importantly, of germline specification and migrating PGCs (Stella, Prdm14, Fragilis, Blimp1, Nanos3, and Dnd1) [64,65]. The expression of some of these crucial genes has subsequently been confirmed by demonstrating the presence of transcriptionally active promoters in these genes.…”