Skin regeneration and repair
cédric Blanpain
Different types of stem cell maintain the skin’s epidermis and contribute to its healing after damage. The identity of a stem-cell type that gives rise to different epidermal-cell lineages has just been revealed.
Skin acts as an essential barrier, protecting organisms from their environment. It is composed of two parts: the epidermis, the cells of which form the barrier; and the dermis, which provides support and nutrition to the epidermis. The epidermis also produces appendages, including sweat glands, and hair follicles and their associated sebaceous glands. The different epidermal compartments undergo constant cellular turn over to replace the dead or damaged cells. This homeostatic process is thought to involve several types of stem cell, each located in a specific epidermal region and contributing to the maintenance of a discrete compartment of the skin1 (Fig. 1a). In a paper published in Science, Snippert et al. identify the “Lgr6” protein as the marker of progenitors that can differentiate into different cell lineages of the skin epidermis.
The first evidence that skin stem cells can differentiate into
interfollicular epidermis,
sebaceous gland and hair follicle lineages came from transplantation of bulge stem cells(3,4) — a cell population located at the base of hair follicles. Further experiments revealed that, during both embryonic development and normal adult skin homeostasis, bulge stem cells and their progeny contribute to hair-follicle regeneration but not to the maintenance of the interfollicular epidermis(4–6). In conditions such as wounding, however, bulge stem cells rapidly migrate towards the interfollicular epidermis to help with the rapid regeneration of the wounded skin(5,7,8).
Later findings also showed that sebaceousgland cells are maintained by progenitors
located above the bulge, which express the Blimp1 protein during morphogenesis(9).
Maintenance of the interfollicular epidermis, meanwhile, involves many small units of
proliferation scattered throughout this skin layer, called epidermal proliferative units (10,11).
The infundibulum — the upper part of the hair follicle, which interfaces
with the interfollicular epidermis — is thought to be maintained by
progenitors located in a hair-follicle region known as the isthmus; these cells, which express the marker proteins MTS24 and Lrig1 (refs 12–14), can differentiate into all epidermal cell lineages after transplantation(13,14). Snippert et al.2 set out to identify the ‘mother’ of these epidermal stem cells. They find that, during skin formation in mice, the transmembrane receptor Lgr6 is expressed in both the hair follicle and the interfollicular epidermis. In adult animals, however, Lgr6 expression becomes restricted to the isthmus, where about
one-third of Lgr6-marked cells also express MTS24 and a few co-express Blimp1.
To more precisely define the differentiation potential of
Lgr6-expressing cells, the authors used genetic wizardry to permanently label Lgr6-expressing cells and their progeny. As expected from the first set of results2, as well as previous data6,8, Lgr6-expressing cells gave rise to cells of both the hair follicle and the sebaceous
gland during embryonic development. Moreover, some cells of the interfollicular
epidermis were derived from Lgr6-expressing cells (Fig. 1b).
The authors’ lineage tracing of adult skin shows that Lgr6 labelling was initially restricted mainly to the cells of the isthmus region, with some labelling of cells in the interfollicular epidermis and other parts of the hair follicles, albeit at lower frequency. Two months later, Lgr6 progeny were found mainly in the isthmus and sebaceous gland, with some in the interfollicular epidermis, and more rarely elsewhere in the hair follicle. These findings suggest that Lgr6-expressing cells contribute mostly to the homeostasis of the isthmus region and the sebaceous gland, whereas a few may have the potential to differentiate into other epidermal lineages. It remains unclear whether a single subpopulation within the Lgr6-marked cells regenerates both the isthmus and sebaceous
gland or whether Lgr6 is expressed in both the previously
identified12–14 isthmus progenitors expressing Lrig1 and MTS24, and the Blimp1- expressing sebaceous-gland progenitors(9).Snippert et al. also find that, like isthmus stem cells13,14, Lgr6-expressing cells transplanted into immunodeficient mice give rise to all epidermal cell lineages. Moreover, like bulge stem cells, Lgr6-expressing stem cells are activated by wounding and migrate towards the epidermis to aid wound repair (Fig. 1b). These
intriguing observations suggest that at least two different hair-follicle stem-cell populations can
actively contribute to the repair of the damaged epidermis.
The presence of Lgr6-derived cells in theinterfollicular epidermis during tissue homeostasisis more puzzling. According to previouscell-lineage tracing of embryonic skin6,8,all cells of the mature hair follicle, includingthose of the isthmus region, are derived fromcells expressing two other progenitor markers,Shh and Sox9. By contrast, the interfollicularepidermis is not labelled with these markersunless wounded, suggesting little or no contributionof hair-follicle cells to the maintenanceof the interfollicular epidermis6,8.Three scenarios could explain Snippert andcolleagues’ observation that Lgr6-derived cellsare present in the interfollicular epidermis.
节选自nature的一片研究生英语面试翻译的文章
