No abstract

The workshop on Hair Follicle Stem Cells brought together investigators who have used a variety of approaches to try to understand the biology of follicular epithelial stem cells, and the role that these cells play in regulating the hair cycle. One of the main concepts to emerge from this workshop is that follicular epithelial stem cells are multipotent, capable of giving rise not only to all the cell types of the hair, but also to the epidermis and the sebaceous gland. Furthermore, such multipotent stem cells may represent the ultimate epidermal stem cell. Another example of epithelial stem cell and transit amplifying cell plasticity, was the demonstration that adult corneal epithelium, under the influence of embryonic skin dermis could form an epidermis as well as hair follicles. With regards to the location of follicular epithelial stem cells, immunohistochemical and ultrastructural data was presented, indicating that cells with stem cell attributes were localized to the prominent bulge region of developing human fetal hair follicles. Finally, a new notion was put forth concerning the roles that the bulge-located stem cells and the hair germ cells played with respect to the hair cycle.

IntroductionTwo major obstacles to the study of adult somatic stem cells are the paucity of specific selection markers and our current inability to understand fully the controls of stemness and to exploit the capacity for stem cell self-renewal. In two previous issues of J. Cell Sci. (Fortunel et al., 1998;Batard et al., 2000), we have introduced the working model of high proliferative potential-quiescent (HPP-Q) cells to refer to primitive human hematopoietic progenitor cells, on which transforming growth factor-β1 (TGF-β1) exerts an important regulatory role. According to this model, (1) TGF-β1 maintains these cells in a quiescent or slow-cycling state, in part by downmodulating various cytokine receptors, resulting in a mitogenic receptor low phenotype, and thus providing a tool to select this subpopulation (Fortunel et al., 1998); and (2) TGF-β1 may also participate in the control of hematopoietic stem/progenitor cell immaturity. This second function is suggested by the fact that TGF-β1 maintains a high level of the cell-surface expression of hematopoietic cell immaturity markers, such as CD34, throughout successive divisions (Batard et al., 2000). However, because hematopoietic stem and progenitor cells spontaneously differentiate into several lineages and do not remain as a homogenous population in culture, it appeared complex to study the effect of TGF-β1 on long-term selfrenewal in this system. As presented in this report, we found that the human epidermal precursor cell compartment represents a unique model to analyze the effect of TGF-β1 on long-term self-renewal of functional undifferentiated somatic cells.Most studies performed to identify cell-surface markers expressed by primitive keratinocytes have focused on molecules involved in cell adhesion. It has been reported that early keratinocytes of the basal layer of the epidermis express the α2β1 and α3β1 integrins (Peltonen et al., 1989; Carter et 4043We have previously introduced the concept of high proliferative potential-quiescent (HPP-Q) cells to refer to primitive human hematopoietic progenitors, on which transforming growth factor-β1 (TGF-β1) exerts a pleiotropic effect. TGF-β1 confers to these slow-dividing cells a mitogenic receptor low phenotype and maintains immature properties by preventing differentiation and apoptosis. However, the effect of TGF-β1 on long-term expansion has not yet been clearly demonstrated. Here, we describe the characterization of a human skin keratinocyte subpopulation, highly enriched for primitive epidermal precursors, on the basis of high adhesion capacity (Adh +++ ) and low expression of the epidermal growth factor receptor (Adh +++ EGF-R low ). In our standard culture condition without feeder cells, the mean estimated output for cells from an unfractionated population of primary foreskin keratinocytes was 10 7 -10 8 , increasing to 10 12 -10 13 in cultures initiated with selected Adh +++ EGF-R low precursors. Characterization of these cells revealed a hitherto unknown property of TGF-β1: its addition at a very l...