Therefore, cells that are actively cycling often mitotic appear to initiate terminal differentiation (Fig. 10).
We show that actively cycling keratinocytes of normal skin initiate terminal differentiation without suppressing DNA replication and become polyploid.
It appears the proliferating cells located on the periphery of the gland continued dividing but their progeny were unable to initiate terminal differentiation.
Traditionally, proliferative keratinocytes have been assumed to exit the cell cycle into G0 (cell growth arrest) before they initiate terminal differentiation.
The strikingly similar effects of Myc and TSA in stimulating proliferation followed by differentiation strongly suggest that histone hyperacetylation is part of the mechanism by which keratinocytes initiate terminal differentiation [11], [41].
Human interfollicular epidermal stem cells express high levels of ß1 integrins and are arranged in clusters in the epidermal basal layer, surrounded by their progeny, transit amplifying (TA) cells, and cells that have initiated terminal differentiation.
Since mammalian erythropoiesis involves proliferation, chromatin changes, and cell-cycle exit to initiate terminal differentiation to mature RBCs, we hypothesized that Chk1+/− erythroblasts also might accumulate DNA damage during RBC differentiation.
As keratinocytes leave the basal layer and initiate terminal differentiation, their intermediate filament cytoskeleton changes from proliferative keratins 5 and 14 to the post-mitotic keratins 1 and 10 [5], [6], [6].
On the other hand, since the knockdown of RNF10 in Schwann cells induced cell proliferation, we conjecture that RNF10 may be involved in exiting from cell cycle to initiate terminal differentiation and myelination.
The ability to heal wounds relies on the rapid migration and proliferation of epithelial cells located in the basal layer of the epidermis adjacent to the area of tissue damage, and their ability to initiate terminal differentiation programs that result in the replenishment of the spinous, granular, and ultimately the cornified layers of the stratified epithelium [2][7].
