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Hair & Hair Growth Desmond J. Tobin 1 Hair & Hair Growth Desmond J. Tobin Hair & Hair Growth Desmond J. Tobin PhD Dir: Centre for Skin Sciences, University of Bradford 1 Structure of presentation Part I • Biologic value of hair: in context of skin & its appendages • Hair follicle: a multi-cell type ‘mini-organ’ • Hair fibre: the hair follicle’s main secreted product • Hair follicle development & growth: a rare example of life-long activity cycling • Hair follicle as regeneration toolkit: stem cells & plasticity Part II • Hair as a sensor: hair follicle is hard-wired to core neuro-endo-immuno axes • Hair follicle pigmentation: an excellent aging model 2 • Hair growth: some common disorders Biologic value of hair: in the context of the skin 3 The screen versions of these slides have full details of copyright and acknowledgements 1 Hair & Hair Growth Desmond J. Tobin Biologic value of skin & hair Skin: • Biologic barrier and the fluctuating environmental interaction • Recognizes, discriminates & integrates signals (via immune, pigmentary & neuroendocrine systems etc.) Hair follicle (HF): • Protection: trauma, radiation, insects, insulation, and cleansing skin surface • Sensory: environment perception, communication (visual, odorant etc.) • Maintenance: reservoir of many regenerative cells types • Immune: anti-microbial upper HF & sebaceous gland 4 I’ve hair, therefore I am…a mammal • Simple HFs: humans, horses, cattle, pigs, sheep, rodents etc. Single hair fiber from single canal. Retained fibers (mouse) • Compound: dogs & cats. Several growing hairs in 1 canal Often 1o or guard fibers with smaller 2o undercoat fibers • Synchronous: wave-like e.g. Most rodents when young • Mosaic: asynchronous – humans, mice etc. with age • Telogenic: most mammals – continuous growth set by seasonality & then efficient retention of telogen hair fibers • Anagenic: rare (wounding response?) ~90% of human scalp HF hair to be cut. Some animals (e.g. poodle, angora etc.) 5 Humans: so-called ‘naked’ ape Why are humans a bit different? A case of ‘terminal decline’ – evolution transformed terminal HF to vellus 1) Mate selection? Lower infestations? Mark Pagel (Uni of Reading) & Walter Bodmer (Oxford Uni) 2) Sweating advantage of having vellus not terminal hair – greater evaporation potential when hunting (Nina Jablonski) 6 The screen versions of these slides have full details of copyright and acknowledgements 2 Hair & Hair Growth Desmond J. Tobin Some basic hair facts 1) ~5M (2% scalp). vs. black: blonde/brown ↑20%, red ↓20% 2) Types: Lanugo (>1 mm x <0.05 mm); Vellus (1 mm x <40 µm) Terminal (>1 mm x ↑ 0.12 mm) 3) ~500/cm2 on scalp. Africans/Asians < Caucasians Highest density on nose tip/cheek/forehead 4) Mongoloid - circular, Caucasian - oval, African - elliptical 5) Growth ~1cm/month (scalp) – cutting/shaving no effect 6) Scalp hair grows ↑ 10y (1.5 M) ~12wks (arm), 26wks (leg) 7) Normal scalp sheds ≈100 hairs/day 8) Scalp HF cycles about 10-20 times/average life 7 The hair follicle: a multi-cell type ‘mini-organ’ 8 Hair follicle at organism level • A ‘mini-organ’ with multiple cell types and with own blood, nerves, immune & muscle systems • Source & target of numerous hormones • Cycles in cell division, differentiation & death Only adult tissue to do so! HS HF Key: HS = hair shaft HF = hair follicle BV = blood vessel BV 9 The screen versions of these slides have full details of copyright and acknowledgements 3 Hair & Hair Growth Desmond J. Tobin Skin surface: barrier but also ‘open’ system ↑5 million Sweat Gland pores • Sterile electrolytes, metals etc. • Anti-microbials, proteases, growth factors, cytokines, Igs...) • Regulation - emotion/environment • 100 ml to 10 L /day of sweat ~5 million Hair follicles • Vellus, Sebaceous, Terminal HFs • ↑500/cm2 and Highly innervated • Neuroendocrine Axes • Terminal ~3 mm deep vs. Vellus 1 mm 10 Different hair follicle types in the adult human Vellus HF Sebaceous HF Terminal HF 11 The hair fiber /shaft: HF’s main secreted product – variation in type & density across body 12 The screen versions of these slides have full details of copyright and acknowledgements 4 Hair & Hair Growth Desmond J. Tobin Human hair shaft / fiber HS IRS IRS Cu HCu Co ORS d ICu Fiber surface by SEM HCu HS HCu Me ICu Ref: Hair in toxicology: Key: HS = hair shaft; IRS = inner root sheath an important biomonitor; DJ Tobin, Royal Society of Chemistry 2005 ORS = Outer root sheath; HCu = HS cuticle 13ICu = IRS cuticle; Me = Medulla Hair needs mechanical stability: breakdown of nuclear DNA appears crucial Key: WT= wildtype KO = knockout Me = melanin Ref: Fischer H, Tobin DJ et al. Essential role of the keratinocyte-specific endonuclease 14DNase1L2 in the removal of nuclear DNA from hair and nails; J Invest Dermatol 2011 One hair follicle – but many hair types Same hair follicle produces hairs differing in: calibre, length, colour Terminal In utero – Lanugo 15 Vellus The screen versions of these slides have full details of copyright and acknowledgements 5 Hair & Hair Growth Desmond J. Tobin Variation in hair follicle density 300 250 200 150 100 Average HFs/cmAverage 50 0 Forehead Back Thorax Upper Forearm Thigh Calf arm 16Ref: Otberg N et al. Variations of hair follicle size & distribution in different body sites, J Invest Dermatol. 2004 Hair follicle development & growth: a rare example of life-long cyclic activity 17 Hair follicle morphogenesis (1) Stage 1 Stage 2 Stage 3/4 Stage 4 Stage 5 KC DC SG FDP IRS BG FDP FDP IRS KC MEL FDP DC KC DC IRS IRS Refs: Hair in toxicology: an important biomonitor; MEL DJ Tobin, Roy, Soc Chem 2005; Paus R et al. FDP A comprehensive guide for the recognition & classification of distinct stages of hair follicle FDP morpho-genesis, J Invest Dermatol. 1999 FDP Key: KC = keratinocyte; DC = dermal condensation FDP = follicular dermal papilla; IRS = Inner root sheath 18SG = sebaceous gland; Mel = melanocyte; BG = bulge The screen versions of these slides have full details of copyright and acknowledgements 6 Hair & Hair Growth Desmond J. Tobin Hair follicle morphogenesis (2) Stage 6 Stage 8 HS SG HS IRS BG SG BG MEL IRS HS MEL IRS FDP FDP FDP MEL Ref: DJ Tobin Hair in toxicology: an important biomonitor Roy Soc Chem 2005 FDP Stage 8 Key: KC = keratinocyte; FDP = follicular dermal papilla IRS = Inner root sheath; HS = hair shaft; SG = sebaceous gland 19Mel = melanocyte; BG = bulge The hair follicle growth cycle Telogen/ Early Anagen early Anagen DP signals to Epithelium DP signals (e.g. KGF, HGF) to Stem Cells Epithelium signal (e.g. β-catenin) to DP (e.g. WNT) Anagen onset Epithelium Proliferation (e.g. STAT) (e.g. SHH, IGF-1, HGF) Full Anagen Catagen Inducers (e.g. IGF-1, HGF, (e.g. FGF5, TGFβ1, 2, GDNF, NGF?) p75NTR, NT3, VDR, Hair Shaft IFNγ, IL-1, Prolactin Differentiation (+R), Hairless) (e.g. WNT, LEF1, BMP, Notch, FOXN1) Refs: Alonso L, Fuchs E., The hair cycle, J Cell Sci. 2006; Enshell-Seijffers D et al. beta-catenin activity in the dermal Tobin DJ. The genetically-programmed hair growth papilla regulates morpho-genesis and regeneration of hair 20cycle & alopecia, Expert Rev Dermatol 2006 Dev Cell 2010 Hair cycle: test-tube of cell division, differentiation Early Catagen & death Full DP Ref: Magerl M, Tobin DJ et al. Patterns of proliferation and apoptosis Anagen during murine hair follicle morphogenesis, J Invest Dermatol 2001 Mid next anagen Telogen HS Late Catagen CH CH Earliest next anagen BG CH HS ES SG DP TA DP DP DP 21 Mx The screen versions of these slides have full details of copyright and acknowledgements 7 Hair & Hair Growth Desmond J. Tobin Modulation of hair follicle vasculature & hair cycle CD31 (PECAM-1) yellow Catagen Skin CD31 (Red) + TUNEL (Green) Anagen Skin Te lo ge n S ki n Anagen Skin Ki67 Red Ref: Mecklenburg L, Tobin DJ et al. Active hair growth 22CD31Green is associated with angiogenesis, J Invest Dermatol 2000 Fibroblast dynamics during hair growth cycle CTS & DP 3 Mitosis 2 4 Anagen III/IV Anagen II CTS & DP 1 Mitosis 6 Anagen VI CTS 5 Mitosis 7 Anagen I CTS Apoptosis CTS Catagen III Telogen Apoptosis Catagen VI Refs: Tobin DJ et al. Plasticity and Cytokinetic Dynamics of the hair follicle mesenchyme, J Invest Dermatol 2000. Chi W, Wu E, Morgan BA, Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline, 23Development 2013 Hair growth cycle directs hair pigmentation Variable states of melanocyte quiescence, melanogenic activity, senescence, & apoptosis BULGE SG APM IRS ORS AL MITOSIS Telogen Early FP Late Anagen Catagen Mid Early Catagen Full Catagen Anagen Refs: Tobin DJ et al. Do hair bulb melanocytes undergo apoptosis during hair follicle regression, J Invest Dermatol 1998; Slominski et al. Hair follicle pigmentation, J Invest Dermatol 2005; Commo S & Bernard BA., Melanocyte subpopulation turnover during 24FP the human hair cycle: an immunohistochemical study, Pigment Cell Res. 2000 The screen versions of these slides have full details of copyright and acknowledgements 8 Hair & Hair Growth Desmond J. Tobin Hair cycle induction/regression mediators Anagen • Trauma: e.g. plucking, depilation; releases inflammatory mediators? • Growth factors: many & varied • Drugs: minoxidil, cyclosporin, tretinoin etc. Catagen • Stress: e.g. psycho-social • Hormones: e.g. estrogen & glucocorticosteroids • Growth factors: many & varied 25 The hair follicle - a regeneration toolkit: stem cells & plasticity Intense evolutionary selective pressure to maintain coat; so unsurprising that HF jam-packed with regenerative capacity 26 Stem cells & hair cycle • HF stem cells are activated at the telogen-to-anagen transition, to initiate new round of hair growth • From reservoir of multi-potent epithelial stem cells in lowest permanent portion of HF, i.e. ‘bulge’ • Lower portion of HF regenerates to produce new hair • stem cells important for maintenance of sebaceous gland • Stem cells respond to epidermal wounding by generating short- lived 'transit amplifying' cells for acute wound repair Refs: Ito M et al.
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