Dedifferentiation-derived cells exhibit phenotypic and functional characteristics of epidermal stem cells

Abstract

Differentiated epidermal cells can dedifferentiate into stem cells or stem cell-like cells in vivo. In this study, we report the isolation and characterization of dedifferentiation-derived cells. Epidermal sheets eliminated of basal stem cells were transplanted onto the skin wounds in 47 nude athymic (BALB/c-nu/nu) mice. After 5 days, cells negative for CK10 but positive for CK19 and β1-integrin emerged at the wound-neighbouring side of the epidermal sheets. Furthermore, the percentages of CK19 and β1-integrin+ cells detected by flow cytometric analysis were increased after grafting (P < 0.01) and CK10+ cells in grafted sheets decreased (P < 0.01). Then we isolated these cells on the basis of rapid adhesion to type IV collagen and found that there were 4.56% adhering cells (dedifferentiation-derived cells) in the grafting group within 10 min. The in vitro phenotypic assays showed that the expressions of CK19, β1-integrin, Oct4 and Nanog in dedifferentiation-derived cells were remarkably higher than those in the control group (differentiated epidermal cells) (P < 0.01). In addition, the results of the functional investigation of dedifferentiation-derived cells demonstrated: (1) the numbers of colonies consisting of 5–10 cells and greater than 10 cells were increased 5.9-fold and 6.7-fold, respectively, as compared with that in the control (P < 0.01); (2) more cells were in S phase and G2/M phase of the cell cycle (proliferation index values were 21.02% in control group, 45.08% in group of dedifferentiation); (3) the total days of culture (28 days versus 130 days), the passage number of cells (3 passages versus 20 passages) and assumptive total cell output (1 × 105 cells versus 1 × 1012 cells) were all significantly increased and (4) dedifferentiation-derived cells, as well as epidermal stem cells, were capable of regenerating a skin equivalent, but differentiated epidermal cells could not. These results suggested that the characteristics of dedifferentiation-derived cells cultured in vitro were similar to epidermal stem cells. This study may also offer a new approach to yield epidermal stem cells for wound repair and regeneration.

Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs

“…Fu et al showed that normal human skin cells de-differentiated into stem cells in the presence of EGF. [30][31][32] Chaffer et al also demonstrated that CD44lo basal-like human mammary epithelial cells and the transformed epithelial cells could all spontaneously de-differentiated into CD44hi stem cells and CD44hi CSCs respectively, and the convertion of transformed epithelial cells to CSCs was more efficiently than the untransformed cells. 33 The conversion of bulk cancer cells into CSCs may be simpler due to the genomic instability of cancer cells.…”

Dedifferentiation of Human Terminally Differentiating Keratinocytes into Their Precursor Cells Induced by Basic Fibroblast Growth Factor

“…18) We previously found that the recombinant human epidermal growth factor could induce the reversion of differentiated epidermal cells into stem cells or stem cell-like cells in vivo. 19,20) Therefore, extrinsic factors in the cellular environment can influence the developmental fate of somatic epidermal keratinocytes, and we can achieve dedifferentiaton by remodeling a microenvirnoment composed of intrinsic and extrinsic cellular molecules.…”

Differentiated Epidermal Cells Regain the Ability to Regenerate a Skin Equivalent by Increasing the Level of β-Catenin in the Cells

“…The dedifferentiation phenomenon of differentiated epidermal cells which dedifferentiated into stem cells or stem cell-like cells in the wound treated with recombinant human epidermal growth factor has already been reported [Fu et al, 2001]. In succedent researches, the model of epidermal cell dedifferentiation in vivo was constructed and dedifferentiation-derived stem cells were isolated [Zhang et al, 2010]. Thus, abundant epidermal stem cells can be generated using an efficient dedifferentiation process involving manipulation of the related pathways.…”