Mouse epidermal stem cells proceed through the cell cycle

Abstract

The epidermis is a continuously renewing tissue maintained by undifferentiated stem cells. For decades it has been assumed that epidermal stem cells (ESCs) were held in the G0 phase of the cell cycle and that they only entered the cell cycle when needed. Previously, we showed that ESCs retained nuclear label for long periods, indicating that these cells did not proceed through the cell cycle at the same rate as the other proliferative basal cells. However, their exact cell-cycle profile has not been determined because a pure population of ESCs has not been available. In this study, we sorted stem and transient amplifying (TA) cells from murine neonatal back skin, and adult ear, footpad, and back skin, using our recently developed method. We found that neonatal back skin had two times the number of ESCs as the adult tissues. Despite the age and anatomical difference, these ESC populations exhibited similar cell cycle profiles with approximately 96% in G0/G1 and 4% in S-G2/M. The cell cycle profiles of the TA cells from neonatal back skin and adult footpad also showed a profile similar to each other (85% in G1 and 15% in S-G2/M). Examination of genes on a cell cycle chip showed that proliferation associated genes and only p57 were upregulated in the TA cell and ESC population, respectively. We found BrdU positive and cyclin B1 positive cells in all groups, confirming that both ESCs and TA cells were cycling. These data demonstrate that there are more TA cells dividing than ESCs, that the cell cycle profile of adult TA cells is related to the proliferative state of the tissue in which they reside, and that ESC proceed through the cell cycle.

The CDK inhibitors: potential targets for therapeutic stem cell manipulations?

“…11 In the skin, four times as many dermal stem cells are in the S-G 2 /M phases of the cell cycle as compared to more primitive dermal cells. 12 In the central nervous system, quiescent neural stem cells (NSCs) quickly proliferate in response to ischemic injury in an attempt to repair damaged tissue. 13,14 This quiescent phenotype necessary to prevent premature exhaustion of the repopulating ability of adult stem cells over the lifetime of individual, in coordination with a rapidly dividing progenitor pool responsive to stress conditions, including tissue damage and transplantation, is a fundamental characteristic of tissue stem cells.…”

Gene Expression Signatures of Seven Individual Human Embryonic Stem Cell Lines

“…Interestingly, we found p57 (CDKN1C) to be upregulated over twofold in nonlineage-differentiated cells compared with all hESC lines. p57 is known as a negative regulator of the cell cycle [27,28]. During mouse retinal development, p57 regulates cell-cycle exit coincident with induction of differentiation [29].…”

Epidermal stem cells are resistant to cellular aging

“…EpiSCs cycle infrequently, with over 95% in G0/ G1 of the cell cycle at any given time (Bickenbach, 1981;Dunnwald et al ., 2003). Similar to other somatic stem cells, EpiSCs are assumed to have the ability to undergo asymmetric cell division, a process in which one daughter cell is the regenerated EpiSC, while the other daughter cell is termed a transit-amplifying (TA) cell (Potten et al ., 1978;Sherley, 2002).…”