Epidermal stem cells are resistant to cellular aging
Jackie R. Bickenbach
Departments of Anatomy and Cell Biology and
Dermatology and Pathology, University of Iowa Carver College of Medicine, IA 52242, USA
Search for more papers by this authorJackie R. Bickenbach
Departments of Anatomy and Cell Biology and
Dermatology and Pathology, University of Iowa Carver College of Medicine, IA 52242, USA
Search for more papers by this authorSummary
The epidermis of the skin, acting as the primary physical barrier between self and environment, is a dynamic tissue whose maintenance is critical to the survival of an organism. Like most other tissues and organs, the epidermis is maintained and repaired by a population of resident somatic stem cells. The epidermal stem cells reside in the proliferative basal cell layer and are believed to persist for the lifetime of an individual. Acting through intermediaries known as transit amplifying cells, epidermal stem cells ensure that the enormous numbers of keratinocytes required for epidermal homeostasis to be maintained are generated. This continual demand for new cell production must be met over the entire lifetime of an individual. Breakdown of the epidermal barrier would have catastrophic consequences. This leads us to question whether or not epidermal stem cells represent a unique population of cells which, by necessity, might be resistant to cellular aging. We hypothesized that the full physiologic functional capacity of epidermal stem cells is maintained over an entire lifetime. Using murine skin epidermis as our model system, we compared several properties of young and old adult epidermal stem cells. We found that, over an average mouse's lifetime, there was no measurable loss in the physiologic functional capacity of epidermal stem cells, leading us to conclude that murine epidermal stem cells resist cellular aging.
Supporting Information
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Fig. S1 A long-term culture of old EpiSCs maintained expression of the cell cycle inhibitors p16Ink4a, p19Arf, and p53 through 29 population doublings. EpiSCs were isolated form 29-month-old mice and grown in culture. After 6 months and 29 PDs, RT-PCR was performed to detect expression of the indicated genes. Keratin 14 was included as a positive control.
Fig. S2 Early-passage cultures of young and old EpiSCs are responsive to calcium-induced differentiation. EpiSCs were sorted from footpad epidermis of 2- and 29-month-old C57BL/6 mice and grown in culture. Early-passage cultures from old (A-D) and young (E-H) EpiSCs grown in low calcium medium designed to prevent differentiation were stained for keratin 14 (K14), keratin 1 (K1), and filaggrin (all red). Cultures from old (I-L) and young (M-P) EpiSCs exposed to a medium containing 1.2 mm Ca2+ designed to induce epidermal differentiation are stained for K14, K1, and filaggrin. Nuclei are counterstained with DAPI (blue). Young cells are passage 4 (PD = 2.3); old cells are passage 3 (PD = 1.8). Magnification = ×100 (phase); ×400 (K14, K1, and filaggrin).
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