Abstract
Keratinocytes isolated from human epidermis and subsequently cultured may form clones if they are 11 micron or less in diameter but are irreversibly committed to further enlargement and terminal differentiation if they are 12 micron or more in diameter. When a founding cell of 11 micron or less forms a small rapidly growing clone in culture, the cells of that clone are able to found new colonies even when their diameter is as great as 20 micron. As the clone becomes larger and grows more slowly, the maximal size of its clonogenic cells is reduced toward that of the epidermis. A cultured cell of up to 20 micron in diameter can, when it divides, give rise to clonogenic progeny smaller than itself, thus reversing the process of enlargement. Cells larger than 20 micron cannot divide and therefore cannot be rescued from terminal differentiation. It is concluded that when keratinocytes multiply rapidly, they extend reversibly the maximal size at which they are capable of generating clones into the range usually characteristic of terminally differentiating cells. It is proposed that this mechanism enables the keratinocyte to accommodate an increased rate of multiplication to its need to attain a large size during terminal differentiation.
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- Al-Barwari S. E., Potten C. S. Regeneration and dose-response characteristics of irradiated mouse dorsal epidermal cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1976 Sep;30(3):201–216. doi: 10.1080/09553007614550981. [DOI] [PubMed] [Google Scholar]
- Allen-Hoffmann B. L., Rheinwald J. G. Polycyclic aromatic hydrocarbon mutagenesis of human epidermal keratinocytes in culture. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7802–7806. doi: 10.1073/pnas.81.24.7802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Banks-Schlegel S. P., Schlegel R., Pinkus G. S. Keratin protein domains within the human epidermis. Exp Cell Res. 1981 Dec;136(2):465–469. doi: 10.1016/0014-4827(81)90028-8. [DOI] [PubMed] [Google Scholar]
- Banks-Schlegel S., Green H. Involucrin synthesis and tissue assembly by keratinocytes in natural and cultured human epithelia. J Cell Biol. 1981 Sep;90(3):732–737. doi: 10.1083/jcb.90.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bergstresser P. R., Pariser R. J., Taylor J. R. Counting and sizing of epidermal cells in normal human skin. J Invest Dermatol. 1978 May;70(5):280–284. doi: 10.1111/1523-1747.ep12541516. [DOI] [PubMed] [Google Scholar]
- Dover R., Potten C. S. Cell cycle kinetics of cultured human epidermal keratinocytes. J Invest Dermatol. 1983 May;80(5):423–429. doi: 10.1111/1523-1747.ep12555494. [DOI] [PubMed] [Google Scholar]
- Fuchs E., Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. doi: 10.1016/0092-8674(80)90094-x. [DOI] [PubMed] [Google Scholar]
- Fuchs E., Green H. Multiple keratins of cultured human epidermal cells are translated from different mRNA molecules. Cell. 1979 Jul;17(3):573–582. doi: 10.1016/0092-8674(79)90265-4. [DOI] [PubMed] [Google Scholar]
- Gallico G. G., 3rd, O'Connor N. E., Compton C. C., Kehinde O., Green H. Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med. 1984 Aug 16;311(7):448–451. doi: 10.1056/NEJM198408163110706. [DOI] [PubMed] [Google Scholar]
- Gelfant S. On the existence of non-cycling germinative cells in human epidermis in vivo and cell cycle aspects of psoriasis. Cell Tissue Kinet. 1982 Jul;15(4):393–397. doi: 10.1111/j.1365-2184.1982.tb01056.x. [DOI] [PubMed] [Google Scholar]
- Gibbs P. E., Freedberg I. M. Epidermal keratin messenger RNAs: a heterogeneous family. Biochim Biophys Acta. 1982 Feb 26;696(2):124–133. doi: 10.1016/0167-4781(82)90019-7. [DOI] [PubMed] [Google Scholar]
- Green H. Cyclic AMP in relation to proliferation of the epidermal cell: a new view. Cell. 1978 Nov;15(3):801–811. doi: 10.1016/0092-8674(78)90265-9. [DOI] [PubMed] [Google Scholar]
- Green H. The keratinocyte as differentiated cell type. Harvey Lect. 1980;74:101–139. [PubMed] [Google Scholar]
- Jordon R. E., Beutner E. H., Witebsky E., Blumental G., Hale W. L., Lever W. F. Basement zone antibodies in bullous pemphigoid. JAMA. 1967 May 29;200(9):751–756. [PubMed] [Google Scholar]
- Lajtha L. G. Stem cell concepts. Differentiation. 1979;14(1-2):23–34. doi: 10.1111/j.1432-0436.1979.tb01007.x. [DOI] [PubMed] [Google Scholar]
- Lavker R. M., Sun T. T. Epidermal stem cells. J Invest Dermatol. 1983 Jul;81(1 Suppl):121s–127s. doi: 10.1111/1523-1747.ep12540880. [DOI] [PubMed] [Google Scholar]
- Lavker R. M., Sun T. T. Heterogeneity in epidermal basal keratinocytes: morphological and functional correlations. Science. 1982 Mar 5;215(4537):1239–1241. doi: 10.1126/science.7058342. [DOI] [PubMed] [Google Scholar]
- Meyer J., Alvares O. F., Barrington E. P. Volume and dry weight of cells in the epithelium of rat cheek and palate. Growth. 1970 Mar;34(1):57–73. [PubMed] [Google Scholar]
- Morhenn V. B., Wood G. S., Engleman E. G., Oseroff A. R. Selective enrichment of human epidermal cell subpopulations using monoclonal antibodies. J Invest Dermatol. 1983 Jul;81(1 Suppl):127s–131s. doi: 10.1111/1523-1747.ep12540890. [DOI] [PubMed] [Google Scholar]
- Morris R., Argyris T. S. Epidermal cell cycle and transit times during hyperplastic growth induced by abrasion or treatment with 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1983 Oct;43(10):4935–4942. [PubMed] [Google Scholar]
- Patterson J. A., Eisinger M., Haynes B. F., Berger C. L., Edelson R. L. Monoclonal antibody 4F2 reactive with basal layer keratinocytes: studies in the normal and a hyperproliferative state. J Invest Dermatol. 1984 Sep;83(3):210–213. doi: 10.1111/1523-1747.ep12263581. [DOI] [PubMed] [Google Scholar]
- Peehl D. M., Ham R. G. Clonal growth of human keratinocytes with small amounts of dialyzed serum. In Vitro. 1980 Jun;16(6):526–540. doi: 10.1007/BF02626466. [DOI] [PubMed] [Google Scholar]
- Potten C. S. Cell replacement in epidermis (keratopoiesis) via discrete units of proliferation. Int Rev Cytol. 1981;69:271–318. doi: 10.1016/s0074-7696(08)62326-8. [DOI] [PubMed] [Google Scholar]
- Resing K. A., Walsh K. A., Dale B. A. Identification of two intermediates during processing of profilaggrin to filaggrin in neonatal mouse epidermis. J Cell Biol. 1984 Oct;99(4 Pt 1):1372–1378. doi: 10.1083/jcb.99.4.1372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977 Feb 3;265(5593):421–424. doi: 10.1038/265421a0. [DOI] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell. 1975 Nov;6(3):317–330. doi: 10.1016/0092-8674(75)90183-x. [DOI] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
- Rheinwald J. G. Serial cultivation of normal human epidermal keratinocytes. Methods Cell Biol. 1980;21A:229–254. doi: 10.1016/s0091-679x(08)60769-4. [DOI] [PubMed] [Google Scholar]
- Rice R. H., Green H. Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell. 1979 Nov;18(3):681–694. doi: 10.1016/0092-8674(79)90123-5. [DOI] [PubMed] [Google Scholar]
- Rowden G. Ultrastructural studies of keratinized epithelia of the mouse. III. Determination of the volumes of nuclei and cytoplasm of cells in murine epidermis. J Invest Dermatol. 1975 Jan;64(1):1–3. doi: 10.1111/1523-1747.ep12540840. [DOI] [PubMed] [Google Scholar]
- Schiller D. L., Franke W. W., Geiger B. A subfamily of relatively large and basic cytokeratin polypeptides as defined by peptide mapping is represented by one or several polypeptides in epithelial cells. EMBO J. 1982;1(6):761–769. doi: 10.1002/j.1460-2075.1982.tb01243.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schweizer J., Goerttler K. Synthesis in vitro of keratin polypeptides directed by mRNA isolated from newborn and adult mouse epidermis. Eur J Biochem. 1980 Nov;112(2):243–249. doi: 10.1111/j.1432-1033.1980.tb07200.x. [DOI] [PubMed] [Google Scholar]
- Simon M., Green H. Enzymatic cross-linking of involucrin and other proteins by keratinocyte particulates in vitro. Cell. 1985 Mar;40(3):677–683. doi: 10.1016/0092-8674(85)90216-8. [DOI] [PubMed] [Google Scholar]
- Simon M., Green H. Participation of membrane-associated proteins in the formation of the cross-linked envelope of the keratinocyte. Cell. 1984 Apr;36(4):827–834. doi: 10.1016/0092-8674(84)90032-1. [DOI] [PubMed] [Google Scholar]
- Stanley J. R., Hawley-Nelson P., Poirier M., Katz S. I., Yuspa S. H. Detection of pemphigoid antigen, pemphigus antigen, and keratin filaments by indirect immunofluorescence in cultured human epidermal cells. J Invest Dermatol. 1980 Aug;75(2):183–186. doi: 10.1111/1523-1747.ep12522615. [DOI] [PubMed] [Google Scholar]
- Sun T. T., Green H. Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature. 1977 Oct 6;269(5628):489–493. doi: 10.1038/269489a0. [DOI] [PubMed] [Google Scholar]
- Sun T. T., Green H. Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope. Cell. 1976 Dec;9(4 Pt 1):511–521. doi: 10.1016/0092-8674(76)90033-7. [DOI] [PubMed] [Google Scholar]
- Watt F. M., Green H. Involucrin synthesis is correlated with cell size in human epidermal cultures. J Cell Biol. 1981 Sep;90(3):738–742. doi: 10.1083/jcb.90.3.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinstein G. D., McCullough J. L., Ross P. Cell proliferation in normal epidermis. J Invest Dermatol. 1984 Jun;82(6):623–628. doi: 10.1111/1523-1747.ep12261462. [DOI] [PubMed] [Google Scholar]
- Weinstein G. D., Van Scott E. J. Autoradiographic analysis of turnover times of normal and psoriatic epidermis. J Invest Dermatol. 1965 Oct;45(4):257–262. doi: 10.1038/jid.1965.126. [DOI] [PubMed] [Google Scholar]
- Withers H. R. Recovery and repopulation in vivo by mouse skin epithelial cells during fractionated irradiation. Radiat Res. 1967 Oct;32(2):227–239. [PubMed] [Google Scholar]
- Withers H. R. The dose-survival relationship for irradiation of epithelial cells of mouse skin. Br J Radiol. 1967 Mar;40(471):187–194. doi: 10.1259/0007-1285-40-471-187. [DOI] [PubMed] [Google Scholar]
- Woodcock-Mitchell J., Eichner R., Nelson W. G., Sun T. T. Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol. 1982 Nov;95(2 Pt 1):580–588. doi: 10.1083/jcb.95.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yardley H. J., Goldstein D. J. Changes in dry weight and projected area of human epidermal cells undergoing keratinization as determined by scanning interference microscopy. Br J Dermatol. 1976 Dec;95(6):621–626. doi: 10.1111/j.1365-2133.1976.tb07034.x. [DOI] [PubMed] [Google Scholar]
- Yuspa S. H., Koehler B., Kulesz-Martin M., Hennings H. Clonal growth of mouse epidermal cells in medium with reduced calcium concentration. J Invest Dermatol. 1981 Feb;76(2):144–146. doi: 10.1111/1523-1747.ep12525490. [DOI] [PubMed] [Google Scholar]
- van Joost T. Incidence of circulating antibodies reactive with basal cells of skin in drug reactions. Acta Derm Venereol. 1974;54(3):183–187. [PubMed] [Google Scholar]
- van Neste D., Staquet M. J., Viac J., Lachapelle J. M., Thivolet J. A new way to evaluate the germinative compartment in human epidermis, using [3H]thymidine incorporation and immunoperoxidase staining of 67 K polypeptide. Br J Dermatol. 1983 Apr;108(4):433–439. doi: 10.1111/j.1365-2133.1983.tb04595.x. [DOI] [PubMed] [Google Scholar]

