Transformation of somatic cells into stem cell‐like cells under a stromal niche

Abstract

To study the genomic plasticity of somatic cells without ectopic genetic manipulation, we cultured mouse fibroblasts with ovarian cells, embryonic fibroblasts of different strains, and parthenogenetic embryonic stem cells (ESCs). Of 41 trials, cell aggregation resembling nascent ESC colony from inner cell mass was detected in 9 cases (22%), and 6 cases (67%) yielded fibroblast-derived colonies with ESC morphology. Cells used in coculture provided the critical (P=0.0061) inducing factor for the aggregation. These colony-forming fibroblasts (CFFs) showed similar characteristics to those in ESCs and induced pluripotent stem cells (iPSCs), including pluripotency gene expression, in vitro differentiation, and teratoma formation. Furthermore, CFFs produced somatic chimera, although none showed germline chimerism. CFFs had a tetraploid-like karyotype, and their imprinting patterns differed from parthenogenetic ESCs, thereby confirming their nongermline transmissibility. We observed dysregulation of cell cycle-related proteins, as well as both homologous and heterologous recombination of genomic single-nucleotide polymorphisms in CFFs. Our observations provide information on somatic cell plasticity, resulting in stemness or tumorigenesis, regardless of colony-forming cell progenitors in the fibroblast population. The plasticity of somatic genomes under environmental influences, as well as acquisition of pluripotency by cell fusion, is also implicated.

Identification of Adult Stem Cells in Schwalbe's Line Region of the Primate Eye

“…Comparable ultrastructural characteristics have been observed in other types of stem cells in or outside the eye. 38,39 It has been hypothesized that adult stem cells are maintained in a state of ''stemness'' by the presence of controlled intrinsic and extrinsic factors in their local microenvironment, the so-called stem cell niche. 14 Factors that are required for such a niche are extracellular matrix components and cell-cell contacts.…”

Regenerative Medicine and Tissue Engineering in Reproductive Medicine

“…[55][56][57][58] Related to this hypothesis, some authors have even postulated a relationship between the existence of stem cells in the ovarian surface epithelium (OSE) and the incidence of ovarian cancer of epithelial cell origin, a theory that is supported by the deregulation of cell cycle and cell signaling genes which has previously been observed. One of the possible explanations for the existence of germinal stem cells in mammalian ovaries is an ovarian cell dedifferentiation process that, under specific in vitro conditions, produces cells which are able to develop into germ-like cells in the same way as previously described for other cell types.…”

Ovarian germline stem cells: an unlimited source of oocytes?

“…Whether or not adult ovarian GSCs isolated to date represent true oogonial stem cells, attention will most certainly turn to the question of whether they are relevant clinically. Some have argued that the mammalian ovarian GSCs isolated thus far are possibly dedifferentiated cells that then have the potential to develop as germ cells under specific in vitro conditions (71), with the phenomena of dedifferentiation being reported in other cell types (75–77). An alternative to dedifferentiation was proposed based on studies describing the presence of very small embryonic-like (VSEL) stem cells in several adult tissues, including bone marrow and the gonads (78).…”