In-vivo dedifferentiation of keratinocytes to epidermal stem cells

Author's reply Sir—Stem cells can sometimes be identified by their morphology or location. In the Drosophila gonad and peripheral nervous system, for example, stem and non-stem cells have a well defined orientation in relation to the surrounding cells. However, in many tissues, the position of the stem cells is known only roughly, and panels of molecular markers have been developed to define the stem-cell compartment or pool. Little is known about epidermal stem cells because of the absence of specific distinguishing molecular markers within the germinative or basal layer, although they can be distinguished by their quiescent nature in vivo and their greater overall proliferative capacity than other cells. Although there seems to be an absence of specific molecular markers, it has been reported that there are some makers, including β1, α2 or α3 integrin, keratin 19, keratin 15, and keratin 10 have been used. β1 integrin and keratin 19 are described and commonly used as the specific markers for epidermal stem cells,1Cotsarelis G Kaur P Dhouailly D Hengge U Bickenbach J Epidermal stem cells in the skin: definition, markers, localization and functions.Exp Dermatol. 1999; 8: 80-88Crossref PubMed Scopus (161) Google Scholar although results can be inaccurate and the stem cells and transit amplifying cells cannot be identified with these markers. We are doing further studies in vivo and in vitro to differentiate the stem cells from transit amplifying cells by use of epidermal-type fatty acid binding protein, adhesion molecule a6, a member of the integrin family (a6bri) and mAb 10G7 (10G7dim) markers. Cells with a6bri (+) and 10G7dim (−) are stem cells and cells with a6bri (+) and 10G7dim (+) are transit amplifying cells.2Kaur P Li A Adhesive properties of human basal epidermal cells: an analysis of keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells.J Invest Dermatol. 2000; 114: 413-420Crossref PubMed Scopus (180) Google Scholar, 3Li A Simmons PJ Kaur P Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype.Proc Natl Acad Sci USA. 1998; 95: 3902-3907Crossref PubMed Scopus (421) Google Scholar We hope in these and other studies to identify stem cells, transit amplifying cells, and postmitotic differentiating cells. We agree with Michel Brouard and Yann Barrandon that wound healing is a complex biological process and many cells and regulating factors are involved.4Watt FM Hogan BLM Out of eden: stem cells and their niches.Science. 2000; 287: 1427-1430Crossref PubMed Scopus (1453) Google Scholar Our conclusion about the relation between the epidermal cell reversion and EGF came from our serial identification experiments, including data from normal and different development skin. All our preliminary data support EGF being a regulator in cell reversion, but the accurate mechanisms need to be further studied. In response to Klaus Eisendle and Bernhard Zelger, the biopsy samples were taken from normal control skin and the regenerating epidermis in rhEGF-treated skin ulcers and control treated skin ulcers. Because we took the samples from the different individuals, the epidermal thickness differed. Second, epidermal wound healing involves keratinocyte migration and proliferation from the wound edge, controlled by growth factors, which lead to the morphological difference in regenerating epidermis and normal skin. In granulation tissue, the morphology and the number and arrangement of fibroblasts differed substanially from that in normal dermis. Also, the re-epithelialisation in response to growth factors is a biological process with epidermal-cell regeneration and migration. During this process, the mitogenic effect, cellular numbers and size in the rhEGF-treated group were greatly changed.5Bhora FY Dunkin BJ Batzri S et al.Effects of growth factors on cell proliferation and epithelialization in human skin.J Surg Res. 1995; 59: 236-244Summary Full Text PDF PubMed Scopus (140) Google Scholar These changes may explain why the morphology of cells and their nuclei are different compared with that in normal skin. Also, we noted much thicker epidermis in rhEGF-treated skin ulcers. To compare the staining results probed with the different antibodies in the same site, the biopsy was sectioned serially. The sections in panels B and C came from the two sections, but in the same biopsy and, therefore, are similar. Eisendle and Zelger and Haruki Kume and colleagues question whether the islands are only epidermal ridges. These keratinocytes with β1 integrin and keratin 19 positive staining may migrate from the basal layer to the upper layers because of upward migration. Also, the islands may appear when the biopsy samples are not vertically sectioned or because of sectioning error. However, we excluded these possibilities by sectioning biopsy samples in different directions, and all results supported that these stem cell islands were isolated, bearing no anatomic relation with the epidermal stem cells in the basal layer. However, our findings are preliminary. In-vivo dedifferentiation of keratinocytes to epidermal stem cellsIn the past few years, some spectacular works have raised doubts about many long-standing dogmas in the stem-cell world. In this context, Xiaobing Fu and colleagues (Sept 29, p 1067)1 report a study of a putative epidermal keratinocyte dedifferentiation. Full-Text PDF In-vivo dedifferentiation of keratinocytes to epidermal stem cellsXiaobing Fu and colleagues1 report the occurrence of epidermal stem-cell islands in the regenerating epidermis of recombinant human epidermal growth factor (rhEGF) treated human skin ulcers. Full-Text PDF In-vivo dedifferentiation of keratinocytes to epidermal stem cellsWe think that Xiaobing Fu and colleagues' results1 should be carefully reassessed, because the stem-cell islands they report may be only stem-cells around dermal ridges. Full-Text PDF