Stem Cell Mechanisms in the Skin’s Epidermis
The skin’s interfollicular epidermis (IFE) is essential for body barrier functions, but researchers are still puzzled by the identity and molecular make-up of stem cells that reside within the IFE basal layer. This impairs the ability to study the mechanisms that specifically control IFE stem cells for homeostasis and wound healing and how these mechanisms are affected in skin disease and aging. A classical long-standing model, now controversial, states that stem cells divide more infrequently than their direct progeny to protect their DNA from the chemical stress and potential for mutation associated with replication. Thus, certain stem cells have been traditionally identified in vivo as DNA label retaining cells (LRCs)—cells that maintain the DNA of the parent stem cell—versus non-LRCs, which may divide more frequently. Despite this labeling, markers to test the model directly, in vivo, are lacking.
Tudorita (Doina) Tumbar, Molecular Biology and Genetics, has developed new methods to label LRCs and non-LRCs in the epidermis, finding that they are clustered in distinct territories which are patterned relative to each other and to skin features such as hair follicles and blood vessels. She and her team have isolated LRCs and non-LRCs, defined mRNA expression profiles, and demonstrated that they are molecularly distinct cell types. Tumbar’s data suggests a working hypothesis in which the IFE is heterogeneous, composed of molecularly distinct territories that regenerate at different rates from independent stem cells. Tumbar is now rigorously testing this hypothesis not only in mouse models but also in human skin. The research will provide the missing entry point into characterizing the molecular mechanisms that govern stem cells within this essential, yet surprisingly poorly understood skin compartment. NIH Award Number: 1R01AR070157-01A1