The interfollicular epidermis of the abraded group of mice quickly regenerated from cells in the hair follicles, after which time, tumor promotion with TPA was begun in both groups. Hence, label-retaining cells divide to form colonies (albeit small ones), and they appear to possess greater proliferative potential than do pulse-labeled cells, which form colonies only rarely. While specification of stem cells remains poorly understood, lineage analysis suggests that stem cells in the piloseba‐ceous unit are specified in situ from within the follicular epithelium (17). The persistence and, if anything, increase in the abundance of labeled cells in the wound suggests that this population is at least as effective at maintaining the epidermis as stem cells that originated in the epidermal compartment. Under the right conditions in the body or a laboratory, stem cells divide to form more cells called daughter cells. Holoclone can give rise to meroclone and paraclone but reverse does not happen. Long‐lasting epidermal progenitors arise from the hair follicle after wounding. Bickenbach, JR, McCutecheon, J, Mackenzie, IC. These rare cells, then, represent the target of two-stage carcinogenesis. Because of the nature of this article, I could not give the original citations from the work of my many colleagues, and I ask the reader’s understanding. In some areas of the wound, the labeled basal cells were continuous with the infundibulim of an adjacent hair follicle. Keratinocyte stem cells have not yet been isolated, but some of their features are now becoming evident. The healed epidermis consisted of both labeled cells derived from the follicle and unlabeled keratinocytes. It includes constituents of the pilosebaceous epithelium that are not normally derived from the follicular bulge. Mice in which the interfollicular epidermis had been previously removed developed papillomas and carcinomas (25), and carcinoma responses were not significantly different in the abraded and unabraded groups. Academic Press. TA cells differentiate and give rise to spinous, granular and stratum corneum layers. Following 20 min fixation in 0.2% gluteraldehyde in PBS at 4 degrees the skin pieces were washed and incubated in β ‐galactosidase buffer for 48 h at room temperature. No clear separation is possible with this approach, since pulse-labeled cells are found throughout the gradient, but the densest fraction, which is morphologically characterized by cells with a high nucleus-to-cytoplasm ratio, is enriched for slowly cycling, label-retaining (or carcinogen-retaining) cells, while maturing cells are enriched in lighter fractions.
An intermediate model assumes the epidermis is maintained by a dedicated stem cell‐population but that population is regenerated de novo in wound epithelium from among the cells of the basal epidermis in the healing wound. B) Shh expression is absent in both the telogen hair follicle (arrow head) and interfollicular epidermis 2 days subsequent toa4mmfull‐thickness excisional wound. In fact, human skin aging is thought to be affected by modifications in growth factors and various hormones that decline with age. Recently in The Lancet, Guenou et al. To explore the properties of label-retaining and maturing basal cells in culture, we have prepared keratinocytes labeled in vivo with the familiar procedures of prolonged or brief exposure to [3H]thymidine, and we have cultured these cells on plates of irradiated feeder cell layers for extended periods. The postulated stem cells in the integument are shown in red. In the parlance of the EPU model, it was concluded that follicular cells may act as transient amplifying cells but do not acquire the epidermal stem cell character. No description. Alternative explanations for this phenomenon are discussed below. In the work reported here, we evaluate the lineage label technique used in this analysis and confirm that it remains a reliable indicator of follicular origin in the context of wound healing experiments. Small, ... A.J. However, the relative proportion of labeled cells in the basal layer increased to 37 ± 16%. Keratinocyte stem cells typically divide to maintain homeostasis of epidermal tissue. In addition, the behavior of these cells before, during, and after tumor promotion remains uncertain. By following the distribution of radiolabeled nuclei, we were able to compare the fates of the two subpopulations in vitro (16). Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated.
This was most pronounced at the final time point analyzed (Fig.
Most keratinocyte cell movement is collective rather than singular, as epithelial cells are well attached to each other by cell–cell adhesion structures. By FACS analysis, cells having very high total proliferative output, as expected for stem cells, were α6+/10G7–. Promotion, with an agent such as 12-O-tetradecanoylphorbol-13-acetate (TPA), elicits expression of the neoplastic change, but only in tissue that was previously exposed to mutagenic chemicals or irradiation (for review, see ref. They are an alternative source for regenerative therapies with a potential role in the treatment of several human diseases. Figure 7.4. In Carcinogenesis. Working off-campus? Given this definition, do the targets of carcinogen action meet this definition of a stem cell (5)? Morris, RJ, Fischer, SM, Klein-Szanto, AJP, Slaga, TJ. 5, 7). The scratched 96-well plate can then be tracked by IncuCyte phase contrast live-cell imaging to measure progressive wound closure in each well over time. Nevertheless, several recent developments are extremely promising, such as ex vivo keratinocyte stem cell gene therapy, the capacity to derive adult-like keratinocyte from embryonic stem cells, and the capacity to derive induced pluripotent stem cells from adult keratinocytes. PubMed It is not observed in the permanent portion of the hair follicle, including the follicular bulge stem cells, or in interfol‐licular epidermis. However, after 40 weeks, papillomas were half as numerous in abraded mice.
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