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TISSUE-SPECIFIC STEM CELLS

Stem/Progenitor Cell-Like Properties of Desmoglein 3^dim Cells in Primary and Immortalized Keratinocyte Lines

^aTumour Biology Laboratory,
^bMolecular Oncology Laboratory, Institute of Cancer and CR-UK Clinical Centre, Queen Mary's School of Medicine and Dentistry, Barts and the London, and
^dCentre of Biochemical Pharmacology, William Harvey Research Institute, John Vane Science Center, Charterhouse Square, London, United Kingdom;
^eInstitute of Cell and Molecular Sciences, Queen Mary's School of Medicine and Dentistry, Barts and the London, London, United Kingdom;
^cFACS Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom

Key Words. Desmoglein 3 • Desmosomes • Keratinocytes • Stem cells

Correspondence: Hong Wan, Ph.D., Centre for Clinical and Diagnostic Oral Sciences, Institute of Cell and Molecular Sciences, Blizard Building, 4 Newark Street, Whitechapel, London E1 2AT, United Kingdom. Telephone: +44 (0)20-7014-0408; Fax: +44 (0)20-7014-0401; e-mail: h.wan{at}qmul.ac.uk

Received on May 22, 2006; accepted for publication on January 18, 2007.

First published online in STEM CELLS EXPRESS  January 25, 2007.


We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more "stem/progenitor cell-like" phenotype. Here, we have confirmed that Dsg3^dim cells derived from cultured primary human adult keratinocytes have comparability with ₆^bri/CD71^dim stem cells in terms of colony-forming efficiency. Moreover, these Dsg3^dim cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3^bri cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3^dim cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3^bri and sorted control cells. Dsg3^dim HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3^dim and Dsg3^bri populations. Taken together our data indicate that Dsg3^dim populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features.

Disclosure of potential conflicts of interest is found at the end of this article.

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