**6. Depletion of HFSCs**

character downstream of Wnt and Shh signaling [43]. Nfatc1 colocalizes with other bulge stem cell markers, including CD34, Sox9, Tcf3, and Lhx2 [44]. Nfatc1 mediates HFSC quiescence by transcriptionally suppressing cyclin-dependent kinase 4 (CDK4) expression

**Figure 3.** Distinct stem cell populations in the hair follicle. The hair follicle is divided into the interfollicular epidermis (IFE), infundibulum, junctional zone (JZ)/isthmus, sebaceous gland, bulge, and hair germ. The expressions of proposed stem cell markers at telogen are indicated. Note that the expression domains of these markers dynamically change during hair cycling. A murine hair follicle in telogen is immunostained for keratin 10 (a marker for suprabasal cells, green) and keratin 15 (a marker for bulge stem cells, red). Nuclei are counterstained with 4′, 6-diamidino-2-phenylindole. The

Comparison of the expression profiles of these bulge stem cell markers between the early and late stages in mutant mice demonstrated that the expressions of these markers diminished at later stages or were mislocalized to areas outside the bulge [22, 23]. These results indicate that

Markers that recognize distinct cell populations of the upper (junctional zone) and lower bulge regions have been identified. As mentioned above, Lrig1 is a marker for the junctional zone/ isthmus, which is located between the sebaceous gland and the bulge [30]. Lrig1-expressing

upstream of BMP4 signaling [44].

34 Hair and Scalp Disorders

dotted area indicates the sebaceous gland.

**5.2. Junctional zone/isthmus**

aPKCλ regulates the expression and localization of HFSCs.

HFSCs can be identified as α6-integrin and CD34 double-positive cells with fluorescenceactivated cell sorting (FACS) analysis [48]. Consistent with the decrease in the expression of the bulge stem cell markers at later stages, quantitative FACS analysis demonstrated that the number of α6-integrin/CD34 double-positive cells gradually decreased in aPKCλ cKO mice as the mice aged [22, 23]. Moreover, LRCs in BrdU pulse-chase labeling experiments were severely reduced in the bulge region of the mutant hair follicles [22, 23]. Conversely, the number of Lrig1- or MTS24-expressiong cells was gradually increased [22]. These results indicate that in aPKCλ cKO mice a decrease in quiescent HFSCs is accompanied by an increase of progenitor cells committed to the junctional zone/isthmus and infundibulum.
