Development, Vol 126, Issue 11 2409-2418, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis

UB Jensen, S Lowell and FM Watt
Keratinocyte Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK.

In order to examine the spatial organisation of stem cells and their progeny in human epidermis, we developed a method for whole-mount epidermal immunofluorescence labelling using high surface beta1 integrin expression as a stem cell marker. We confirmed that there are clusters of high beta1 integrin-expressing cells at the tips of the dermal papillae in epidermis from several body sites, whereas alpha6 integrin expression is more uniform. The majority of actively cycling cells detected by Ki67 or bromodeoxyuridine labelling were found in the beta1 integrin-dull, transit amplifying population and integrin-negative, keratin 10-positive cells left the basal layer exclusively from this compartment. When we examined p53-positive clones in sun-exposed epidermis, we found two types of clone that differed in size and position in a way that was consistent with the founder cell being a stem or transit amplifying cell. The patterning of the basal layer implies that transit amplifying cells migrate over the basement membrane away from the stem cell clusters. In support of this, isolated beta1 integrin-dull keratinocytes were more motile on type IV collagen than beta1 integrin-bright keratinocytes and EGFP-labelled stem cell clones in confluent cultured sheets were compact, whereas transit amplifying clones were dispersed. The combination of whole-mount labelling and lineage marking thus reveals features of epidermal organisation that were previously unrecognised.

This article has been cited by other articles:

				F.M. Watt and C.A. Collins Role of {beta}-catenin in Epidermal Stem Cell Expansion, Lineage Selection, and Cancer Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.011v1. [Abstract] [PDF]

				E. Fuchs and J.A. Nowak Building Epithelial Tissues from Skin Stem Cells Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.032v1. [Abstract] [PDF]

				G. W. Neill, W. J. Harrison, M. S. Ikram, T. D.L. Williams, L. S. Bianchi, S. K. Nadendla, J. L. Green, L. Ghali, A.-M. Frischauf, E. A. O'Toole, et al. GLI1 repression of ERK activity correlates with colony formation and impaired migration in human epidermal keratinocytes Carcinogenesis, April 1, 2008; 29(4): 738 - 746. [Abstract] [Full Text] [PDF]

				K. Kadoya, J.-i. Fukushi, Y. Matsumoto, Y. Yamaguchi, and W. B. Stallcup NG2 Proteoglycan Expression in Mouse Skin: Altered Postnatal Skin Development in the NG2 Null Mouse J. Histochem. Cytochem., March 1, 2008; 56(3): 295 - 303. [Abstract] [Full Text] [PDF]

				W. P. Daley, S. B. Peters, and M. Larsen Extracellular matrix dynamics in development and regenerative medicine J. Cell Sci., February 1, 2008; 121(3): 255 - 264. [Abstract] [Full Text] [PDF]

				E. Fuchs Skin stem cells: rising to the surface J. Cell Biol., January 28, 2008; 180(2): 273 - 284. [Abstract] [Full Text] [PDF]

				L. R. Strachan, K. J. Scalapino, H. J. Lawrence, and R. Ghadially Rapid Adhesion to Collagen Isolates Murine Keratinocytes with Limited Long-Term Repopulating Ability In Vivo Despite High Clonogenicity In Vitro Stem Cells, January 1, 2008; 26(1): 235 - 243. [Abstract] [Full Text] [PDF]

				S. Estrach, J. Legg, and F. M. Watt Syntenin mediates Delta1-induced cohesiveness of epidermal stem cells in culture J. Cell Sci., August 15, 2007; 120(16): 2944 - 2952. [Abstract] [Full Text] [PDF]

				A. J. Shortt, G. A. Secker, P. M. Munro, P. T. Khaw, S. J. Tuft, and J. T. Daniels Characterization of the Limbal Epithelial Stem Cell Niche: Novel Imaging Techniques Permit In Vivo Observation and Targeted Biopsy of Limbal Epithelial Stem Cells Stem Cells, June 1, 2007; 25(6): 1402 - 1409. [Abstract] [Full Text] [PDF]

				D. A. Lawson, L. Xin, R. U. Lukacs, D. Cheng, and O. N. Witte Isolation and functional characterization of murine prostate stem cells PNAS, January 2, 2007; 104(1): 181 - 186. [Abstract] [Full Text] [PDF]

				R. E. Davey and P. W. Zandstra Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals an Autoregulatory Stem Cell Niche Stem Cells, November 1, 2006; 24(11): 2538 - 2548. [Abstract] [Full Text] [PDF]

				K. B. Jensen and F. M. Watt Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence PNAS, August 8, 2006; 103(32): 11958 - 11963. [Abstract] [Full Text] [PDF]

				A. Pajoohesh-Ganji, S. Pal-Ghosh, S. J. Simmens, and M. A. Stepp Integrins in Slow-Cycling Corneal Epithelial Cells at the Limbus in the Mouse Stem Cells, April 1, 2006; 24(4): 1075 - 1086. [Abstract] [Full Text] [PDF]

				G. Zerbini, L. Piemonti, A. Maestroni, G. Dell'Antonio, and G. Bianchi Stem Cells and the Kidney: A New Therapeutic Tool? J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S123 - S126. [Abstract] [Full Text] [PDF]

				E. Zcharia, D. Philp, E. Edovitsky, H. Aingorn, S. Metzger, H. K. Kleinman, I. Vlodavsky, and M. Elkin Heparanase Regulates Murine Hair Growth Am. J. Pathol., April 1, 2005; 166(4): 999 - 1008. [Abstract] [Full Text] [PDF]

				L. S. Campos, D. P. Leone, J. B. Relvas, C. Brakebusch, R. Fassler, U. Suter, and C. ffrench-Constant {beta}1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance Development, July 15, 2004; 131(14): 3433 - 3444. [Abstract] [Full Text] [PDF]

				J. Legg, U. B. Jensen, S. Broad, I. Leigh, and F. M. Watt Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis Development, December 15, 2003; 130(24): 6049 - 6063. [Abstract] [Full Text] [PDF]

				S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Endocr. Rev., December 1, 2003; 24(6): 737 - 764. [Abstract] [Full Text] [PDF]

				K. M. Braun, C. Niemann, U. B. Jensen, J. P. Sundberg, V. Silva-Vargas, and F. M. Watt Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis Development, November 1, 2003; 130(21): 5241 - 5255. [Abstract] [Full Text] [PDF]

				F. J. A. Conti, R. J. Rudling, A. Robson, and K. M. Hodivala-Dilke {alpha}3{beta}1-integrin regulates hair follicle but not interfollicular morphogenesis in adult epidermis J. Cell Sci., July 1, 2003; 116(13): 2737 - 2747. [Abstract] [Full Text] [PDF]

				R. Poulsom, M. R. Alison, T. Cook, R. Jeffery, E. Ryan, S. J. Forbes, T. Hunt, S. Wyles, and N. A. Wright Bone Marrow Stem Cells Contribute to Healing of the Kidney J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S48 - 54. [Abstract] [Full Text] [PDF]

				L. Alonso and E. Fuchs Stem cells in the skin: waste not, Wnt not Genes & Dev., May 15, 2003; 17(10): 1189 - 1200. [Full Text] [PDF]

				S L Preston, M R Alison, S J Forbes, N C Direkze, R Poulsom, and N A Wright The new stem cell biology: something for everyone Mol. Pathol., April 1, 2003; 56(2): 86 - 96. [Abstract] [Full Text] [PDF]

				J. P. Seery Stem cells of the oesophageal epithelium J. Cell Sci., January 5, 2002; 115(9): 1783 - 1789. [Abstract] [Full Text] [PDF]

				C. Niemann, D. M. Owens, J. Hulsken, W. Birchmeier, and F. M. Watt Expression of {Delta}NLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours Development, January 1, 2002; 129(1): 95 - 109. [Abstract] [Full Text] [PDF]

				A. Nykjaer, J. C. Fyfe, R. Kozyraki, J.-R. Leheste, C. Jacobsen, M. S. Nielsen, P. J. Verroust, M. Aminoff, A. de la Chapelle, S. K. Moestrup, et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D3 PNAS, November 20, 2001; 98(24): 13895 - 13900. [Abstract] [Full Text] [PDF]

				W. Zhang, E. Remenyik, D. Zelterman, D. E. Brash, and N. M. Wikonkal Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations PNAS, November 9, 2001; (2001) 241353198. [Abstract] [Full Text] [PDF]

				F. Bernerd, D. Asselineau, C. Vioux, O. Chevallier-Lagente, B. Bouadjar, A. Sarasin, and T. Magnaldo Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin invitro PNAS, July 3, 2001; 98(14): 7817 - 7822. [Abstract] [Full Text] [PDF]

				D. W. Borthwick, M. Shahbazian, Q. Todd Krantz, J. R. Dorin, and S. H. Randell Evidence for Stem-Cell Niches in the Tracheal Epithelium Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 662 - 670. [Abstract] [Full Text] [PDF]

				L. M. Coussens and Z. Werb Inflammatory Cells and Cancer: Think Different! J. Exp. Med., March 19, 2001; 193(6): F23 - F26. [Full Text] [PDF]

				F. M. Watt and a. B. L. Hogan Out of Eden: Stem Cells and Their Niches Science, February 25, 2000; 287(5457): 1427 - 1430. [Abstract] [Full Text]

				J. M. Slack Stem Cells in Epithelial Tissues Science, February 25, 2000; 287(5457): 1431 - 1433. [Abstract] [Full Text]

				L. Levy, S. Broad, D. Diekmann, R. D. Evans, and F. M. Watt beta 1 Integrins Regulate Keratinocyte Adhesion and Differentiation by Distinct Mechanisms Mol. Biol. Cell, February 1, 2000; 11(2): 453 - 466. [Abstract] [Full Text]

				C Ferraris, G Chevalier, B Favier, C. Jahoda, and D Dhouailly Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli Development, January 12, 2000; 127(24): 5487 - 5495. [Abstract] [PDF]

				H. Harada, P. Kettunen, H.-S. Jung, T. Mustonen, Y. A. Wang, and I. Thesleff Localization of Putative Stem Cells in Dental Epithelium and Their Association with Notch and FGF Signaling J. Cell Biol., October 4, 1999; 147(1): 105 - 120. [Abstract] [Full Text] [PDF]

				A. J. Zhu, I. Haase, and F. M. Watt Signaling via beta 1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro PNAS, June 8, 1999; 96(12): 6728 - 6733. [Abstract] [Full Text] [PDF]

				W. Zhang, E. Remenyik, D. Zelterman, D. E. Brash, and N. M. Wikonkal Escaping the stem cell compartment: Sustained UVB exposure allows p53-mutant keratinocytes to colonize adjacent epidermal proliferating units without incurring additional mutations PNAS, November 20, 2001; 98(24): 13948 - 13953. [Abstract] [Full Text] [PDF]

				R. M. Lavker and T.-T. Sun Epidermal stem cells: Properties, markers, and location PNAS, December 5, 2000; 97(25): 13473 - 13475. [Full Text] [PDF]