Spatiotemporal coordination of stem cell commitment during epidermal homeostasis

Abstract

Adult tissues replace lost cells via pools of stem cells. However, the mechanisms of cell self-renewal, commitment, and functional integration into the tissue remain unsolved. Using imaging techniques in live mice, we captured the lifetime of individual cells in the ear and paw epidermis. Our data suggest that epidermal stem cells have equal potential to either divide or directly differentiate. Tracking stem cells over multiple generations reveals that cell behavior is not coordinated between generations. However, sibling cell fate and lifetimes are coupled. We did not observe regulated asymmetric cell divisions. Lastly, we demonstrated that differentiating stem cells integrate into preexisting ordered spatial units of the epidermis. This study elucidates how a tissue is maintained by both temporal and spatial coordination of stem cell behaviors.

Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration

“…Conversely, 1 study found no evidence of slow-cycling epithelial stem cells in the mouse esophagus, and suggested that each cell within the basal cell layer is equipotent in generating both proliferating and differentiating cells with equal probability (10). This equipotent model has also been reported for the stratified epithelium of the skin (16).…”

In vivo imaging: shining a light on stem cells in the living animal

“…These observations have led to a model of epidermal stem cell function that is distinct from those previously postulated (Rompolas et al, 2016).…”

“…and marked cells within the epidermis has recently revealed that epidermal stem cells have equal potential to either divide or directly differentiate, a process seemingly coordinated by the fate of sibling cells (Rompolas et al, 2016). These observations have led to a model of epidermal stem cell function that is distinct from those previously postulated (Rompolas et al, 2016).…”

“…The end result is a pool of stem cells that is sufficient for both cellular replacement and hair cell regeneration. The cellular interplay between these processes would not be revealed by the examination of individual stem cells in isolation (Rompolas et al, 2012(Rompolas et al, , 2016 (Fig. 1B).…”

“…This is primarily used to visualise collagen networks in vivo and can consequently provide information on tissue and niche architecture without the need for additional fluorophore labels. The development of this imaging system has allowed, for the first time, the in vivo visualisation of mammalian stem cell populations, in particular in the hair follicle (Rompolas et al, 2012(Rompolas et al, , 2016 and more recently the epidermis (Mesa et al, 2017 preprint).…”