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Skin and Hair Follicular Epithelium
In collaboration with Robert Lavker of Northwestern University, we
discovered that hair follicular epithelial stem cells are located, not in the
matrix area of the hair root as we used to think, but rather in upper hair
follicle in a previously ignored area called the bulge - which is a part of
outer root sheath and marks the lower end of the permanent (upper) portion of
the hair follicle (Cell 1990; 2000). This
finding provided explanations for many paradoxical properties of the hair
follicle including the dispensability of the epithelium of lower follicle in
hair reconstitution assays, and provided for the first time a mechanistic model
explaining the cyclic nature of the follicular growth, i.e., the so-called hair
cycle in which a follicle goes through phases of growing, degenerating and
resting. We proposed that the contact between the normally slow-cycling bulge stem
cells and the dermal papilla cells (a group of highly specialized follicular
mesenchymal cells located at the hair root) during the resting phase plays a
key role in “activating” the epithelial stem cells to undergo proliferation
thereby sending a column of “transit amplifying cells” growing downward forming
a new lower follicle (the “bulge-activation hypothesis”). This hypothesis has
major implications on the relationships among the various keratinocyte lineages
in the skin, the mechanism of hair follicle regulation, and the roles of hair
follicle in skin tumor formation and in a wide range of other skin diseases.
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