Long-term renewal of hair follicles from clonogenic multipotent stem cells

Adult stem cells are essential for tissue renewal, regeneration, and repair, and their expansion in culture is of paramount importance for regenerative medicine. Using the whisker follicle of the rat as a model system, we demonstrate that (i) clonogenicity is an intrinsic property of the adult stem cells of the hair follicle; (h) after cultivation for >140 doublings, these stem cells, transplanted to the dermo-epidermal junction of newborn mouse skin, form part or all of the developing follicles; (fit) the stem cells incorporated into follicles are multipotent, because they generate all of the lineages of the hair follicle and sebaceous gland; (iv) thousands of hair follicles can be generated from the progeny of a single cultivated stem cell; (v) cultured stem cells express the self-renewal genes Bmi1 and Zfp145; (vi) several stem cells participate in the formation of a single hair bulb; and (vii) there are many more stem cells in whisker follicles than could be anticipated from label-retaining experiments.