TERT induction triggers a rapid transition from telogen to anagen. a, Northern blot (left) and TRAP assay (right) show increased TERT expression and telomerase activity by nine days of doxycycline treatment. b, Follicles in i-TERT mice entered anagen (arrow) by day 9, whereas Non-Tg controls remained in telogen (*), H&E, 20x. c, Hair growth was observed only in i-TERT mice (+doxy) (right), but not in i-TERT mice (−doxy) (center) or Non-Tg littermates (left).

TERT's activity in facilitating a transition from telogen to anagen is independent of its function in telomere synthesis. a, TERT induced anagen in mice with TERC+/+, TERC+/−, and TERC−/− backgrounds, H&E 20x. b, Skin samples from i-TERT; TERC−/− mice lacked telomerase activity by TRAP (left) and lacked TERC expression by RT-PCR (right).

Conditional activation of TERT promotes the anagen phase of the hair follicle cycle. a, Diagram of hair follicle cycling b, TRAP on Non-Tg skin samples at days 4, 10 (anagen-A), 16 (catagen-C), 19, 21 (telogen-T), 28, 34 (A), and 52 (T). c–d, Northern blot analysis and TRAP on skin extracts from i-TERT and WT mice at day 50. e, Non-Tg (+doxy) and i-TERT (+doxy) mice at day 70. f, H&E skin sections (*=telogen hair follicle, arrow= anagen hair follicle), 20x. g, RNA in situ hybridization for TERT mRNA and immunofluorescence for K14 in i-TERT (+doxy) skin (*=autofluorescence). h, RNA in situ hybridization for TERT mRNA (blue) in i-TERT(+doxy) skin section (right) and WT anagen skin (left) (*=dermal papilla).

TERT activates stem cells, depleting BrdU label from LRCs. a, Immunofluorescence for BrdU (red) and CD34 (green) shows maintenance of LRCs in Non-Tg group, but dramatic loss of label in i-TERT mice after doxy treatment (pre-doxy = day 55, post-doxy= day 90). b, Quantification of LRC data from (a), showing number of BrdU+ cells/CD34+ cells. i-TERT (black bars, n=4 mice), Non-Tg (gray bars, n=3 mice), - indicates pre-doxy, + indicates post-doxy. c, LRC analysis from whole mounts of epidermis from tail of mice labeled with BrdU at day 10, switched to doxy at day 40 and analyzed at day 65. (BrdU=red, K14=green). d, Immunofluorescence using Ki-67 (red) to mark proliferating cells and K14 (green) to identify basal layer of skin. e, Quantitation of proliferation index in (d) as Ki-67+ cells/100μm length of basal layer. n=2 mice for each comparison. f, GFP epifluorescence costained with CD34 (inset, confocal microscopy) in skin section from an actin-GFP mouse. g, RNA in situ analysis for TERT mRNA in i-TERT(+doxy) mouse skin. (inset) TERT mRNA expression (cytoplasmic) overlaps in bulge with LRCs, marked by BrdU (nuclear). h, H&E sections from K5tTA+; tetop-TERT+ (−doxy) (bottom) and Non-Tg (top) mice, 20X. Error bars indicate standard deviation. p values based on t-test. *=autofluorescence of hair.