Further Development 16.11: The Progenitor Cell Is a Runway Signal

Ectodermal Placodes and the Epidermis

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).

**Figure 1** During hair follicle regeneration, emerging progenitor cells constitute a signaling center that orchestrates tissue growth. The primed stem cells (HFSCs) generate progenitor cells. The quiescent stem cells divide only after the progenitor cells emerge and begin secreting Sonic hedgehog (Shh). Progenitor cell generation diminishes if the progenitors can’t produce Shh. Shh both promotes quiescent stem cell proliferation and regulates the dermal factors that promote progenitor cell expansion. Without input from quiescent HFSCs, replenishment of primed HFSCs for the next hair cycle is reduced. This reduction delays regeneration and can lead to the failure to regenerate the hair follicle. (After Y. C. Hsu et al. 2014. *Nat Med* 20: 847–856.)

Literature Cited

Hsu, Y. C., L. Li and E. Fuchs. 2014. Emerging interactions between skin stem cells and their niches. Nat. Med. 20: 847–856.
PubMed Link

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