Transit-amplifying cell frequency and cell cycle kinetics are altered in aged epidermis
Authors
Charruyer A, Barland CO, Yue L, Wessendorf HB, Lu Y, Lawrence HJ, Mancianti ML, Ghadially R.
Institution
Department of Dermatology, University of California, San Francisco
Country
United States
Year
2009
Journal
Journal of Investigative Dermatology
Abstract
Aged epidermis is less proliferative than young, as exemplified by slower wound healing. However, it is not known whether quantitative and/or qualitative alterations in the stem and/or transit-amplifying (TA) compartments are responsible for the decreased proliferation. Earlier studies found a normal or decreased frequency of putative epidermal stem cells (EpiSCs) with aging. We show, using long-term repopulation in vivo and colony formation in vitro, that, although no significant difference was detected in EpiSC frequency with aging, TA cell frequency is increased. Moreover, aged TA cells persist longer, whereas their younger counterparts have already differentiated. Underlying the alteration in TA cell kinetics in the aged is an increase in the proportion of cycling keratinocytes, as well as an increase in cell cycle duration. In summary, although no significant difference in EpiSC frequency was found, TA cell frequency was increased (as measured by in vivo repopulation, growth fraction, and colony formation). Furthermore, the proliferative capacity (cellular output) of individual aged EpiSCs and TA cells was decreased compared to that of young cells. Although longer cell cycle duration contributes to the decreased proliferative output from aged progenitors, the greater number of TA cells may be a compensatory mechanism tending to offset this deficit.
Product use
Isolation and cultivation of keratinocytes from young and aged mice for chamber implantation experiments, using long-term repopulation in vivo and colony formation in vitro to study quantitative and/or qualitative alterations in the stem and/or transit-am