f)epartrnc nts o f Cd I Uiol o!;y and Neuros cience and "i"De nnatolob'Y. T he University ofTe"as So uthweste rn Medi cal Center at Da lla s. Da lla s. Te"as. U.S .A . Telotnerase is a ribonucleoprotein enzyn"le capable of adding hexanucleotide repeats onto the ends of linear chrotnoSOlnal DNA. Whereas nortnal sOlnatic cells with a litnited replicative capacity fail to express telotnerase activity, Inost in"ln"lortal eukaryotic cells do. Cells of renewal tissues (e.g., skin, intestine, blood)

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... quire an extensive proliferative capacity. Sotne cells in such renewal tissues also express telolnerase activity, Inost likely to prevent rapid erosion of their telotneres during cell proliferation. III this study, we Ineasured the levels of telon"lerase activity in dissected con"lpartInents of the hUlnan hair follicle: hair shaft, gland-containing fraglnent, upper intertnediate fragment (where it is thought undifferentiated stem cells reside), lower intermediate fragtnent, and in the bulb-containing fraglnent (an area with high tnitotic activity containing a more differentiated D urin g the process of cell div isio n. DNA mu sr he fait hfull y re plicated . N o rm al so m atic ce ll s in ve rte bra tes, h oweve r. arc unabl e to compl etely re plic ate the e nds of linear DNA m o le c ul es (O lov niko v, 197 1 ; Wa tso n , "1972), res ultin g in th e sh ortenin g of c hro m oso mal e nds (telomeres) with e ac h ro und of ce U division . Telo m e re s. co mposed of ta nd e m r e peats of the se qu e n ce TTAGGG in ve rte brates (rev ie wed in Blackb urn, 199 1), a re th o u ght to p reve nr d egradation o r abermnt re co mbina tio n of th e c hro m oso mal e n ds (Hastic and Allshire, "1 989; Z akian. 1989). It ha s bee n pro posed that th e e ros io n of telomeres during ce ll di v isi o n is a mi totic cl ock tha t limits the re pli ca tive c apa city of no rmal so matic cell s (Harle y 1'1 (I I, 1990; Shay l'/ (II, 199 4), and the reac hin g of a criti cal telo m e re le n gth signals cell sen escen ce o r ag in g (O lovn ikov. 197 1. 1973; Alls o pp and H arl ey . 1995) . Telo m e rase is a ribonucleoprotein e n zy m e that can us e its RN A component as a te l11plate fo r the addi tio n of teloll1eric repeats to t he e nds of t he c hro m osomes (GI'e ide l ' and Blackburn , 1985, 1987) and. thus, is tho ug ht to co mpe nsa te for te lo m e re erosion . Altho ug h llI os t n or-l11al somatic ce ll s 00 not exp ress relomeras e ac ti vity. its activity is found in ma le rep roduc ti ve ce ll s and in 1110St primary tUlll o rs Manuscript received May 3 (), I ' )<)6; revised August 22 , 1')96; accep led fu r publi cation Septembcr 27. 1996. Rep rin t r cq l1 l!sts to: Dr. Il . Sta l1 Ta y lo r . I)cpat"t tll c ll t o f 1)c nn at() l o~y. Un ive rsit), of Te"as So uthwestern Medi cal Cente r. 5323 Harry Hilles 13oul eva rd . I)a lla s. TX 752:lS-'J{)(,'J. Abb rev iatiom: ITAS. Infernal Tc lolll crase Activity Sta nd ard: T RAP. Tc lo rn cri c R.epeat Amplification Proto co l. pool ofkeratinocytes). In anagen follicles, high levels of telolnerase activity were found aln"lost exclusively in the bulb-containing fragment of the follicles, with low levels of telotnerase in the bulge area (intermediate fragments) and gland-containing fragtnent. In comparison, catagen follicles had low levels of te-100nerase activity in the bulb-containing fragments as well as in other cotnpartments. Such observations indicate that, in anagen hair follicles, the fragments containing cells actively dividing (e.g., transient amplify ing cells) express telomerase activity, whereas fragments containing cells with low mitotic activity, for exalnple, quiescent stem cells, express low levels of telolnerase activity. Kl!JI I/!ovds: stem cells/qlliescell ce/ pl 'o/ijel'atioll/teiomercs. ] [""est Damato/ 108: 113-117, 1997 (Coullter ('( til, 1994 Kim ct ti l, 1994). T he presence oftelol11erase. and subseq ue n t m ainte nan ce of tel o m e re le ngth. im pli cates telomc rase activity as playi n g a ro le in preventin g sen escence III these immor ta li zed ce ll s. Lik ewise, it is tho ug h t that th c e xtreme p ro hfe ra t ive requirements of cell s fo und in ren ewa l tissues su ch as the blood. skin . and intestine wou ld also be capa bl e of cxp resslll g I . . f l " t I·ec 'Il t reports hav c te o m e rase actl\lIry . In support 0 t li S con ce p . l: . . . demon strated the presen ce of te lo m erase activity in he m atopOienc proge nitor cell s a nd activated lymph ocytes (Broccolli ('( tI~, 1995; Hi yam<l C( II I, 1995 ; C hiu ('( til, 1996; Iga ras hi and Sa kaguchi , 1996; Wen g ct (II, 1996). th e epide rmi s (Harle-Bac ho r and Bouka mp, · 1996; Taylo r I't aI, 1996), and the intestin e (Hlyam<l ('( (II, 1996) . T he te lo m e res of cell s ti'o m these tissues , however. a lso declllle w ith d o n o r age (Hastic 1'( ti l. 199 0; Lindsey cI til, 199 1; Va z iri et ti l, 1994 ; Hi yama c ( til, "1 996). suggesting that the level of exp resSIO n of te lo m e rase i.n c e ll s of renewa l tiss ues is suffi Cient to slow. but not_ . T l . Id I' ke l), exrend the life snan o f preve n t, telom e re e rOS IOiI. li S WOll I . . . r th e se ce ll s but wo uld n ot co nfer immo rtali ty. T he h a'ir fo lli cle is a speciali zcd appc ndage of ~le sk.in in whi ch an extraord in aril y hi gh level of pro li fe ratio n. suffiC ient ro Sll~p ort f I . I ' . rQd ll ced fi·om a vc r)' restncted m an y cycles 0 lair g rowt I. IS P . : numh e r of cell s. We h ypothes ize that the speCl ah zed cell popu latio ns respo ll sible fo r rhi s mitoti c activ ity. al'e lik el y ro. e xpress te lOll1 e ra se and t hat te lo ll1 e rasc plays a Criti cal ro le 111 m all1 tall1 l11g ha ir g rowth . T he putative ste m ce ll s I'espo nsibl e to r overa ll fo llt cular h ea lth arc th o u!!;h t to he con cc ntrated Ill . or Just be low. thc bu lge area of the h;~ir fo lli cle (Cotsarclis t't nl, 1990; Yan g C( (II,