Remarkably, activation of the bulge stem cells is regulated in part by the progenitor cells they produce. The progenitor cells secrete Sonic hedgehog, which is essential for the division of the bulge HFSCs. It is possible that the Bmp6 and Fgf signals from these cells inhibit the stem cells beneath the bulge, while their Shh activates the bulge stem cells. This means that the progenitor cells are not merely passive cells on their way to differentiate, but that they constitute a signaling center that can activate the quiescent bulge stem cells (Figure 1; see also Figure 16.17C). The dermal papilla can thereby initiate hair regeneration by stimulating the primed (sub-bulge) HFSCs to establish a population of transit-amplifying cells, and then this progenitor cell population serves as a signaling center to sustain the dermal papilla signaling needed to expand the transit-amplifying cells. These transit-amplifying cells also stimulate proliferation of quiescent stem cells. Thus, the transit-amplifying cells regulate the proliferation of themselves, the primed HFSCs, and the quiescent HFSCs, thereby coordinating the regeneration of the hair follicle (Hsu et al. 2014).
Hsu, Y. C., L. Li and E. Fuchs. 2014. Emerging interactions between skin stem cells and their niches. Nat. Med. 20: 847–856.
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