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This Article Free via Open Access: OA OA Full Text Full Text (PDF) OA All Versions of this Article: 2007-0651v1 26/5/1241    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Lo Celso, C. Articles by Watt, F. M. PubMed PubMed Citation Articles by Lo Celso, C. Articles by Watt, F. M.

TISSUE-SPECIFIC STEM CELLS

Characterization of Bipotential Epidermal Progenitors Derived from Human Sebaceous Gland: Contrasting Roles of c-Myc and β-Catenin

^aMassachusetts General Hospital, Center for Regenerative Medicine, Boston, Massachusetts, USA;
^bCR-UK Cambridge Research Institute, Cambridge, United Kingdom;
^cBarts and The London Queen Mary's School of Medicine and Dentistry, Institute of Cell and Molecular Science, Centre for Cutaneous Research, London, United Kingdom;
^dWellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge, United Kingdom;
^eUniversity of Massachusetts Cancer Center Tissue Bank, Departments of Cancer Biology and Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA;
^fDepartments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany

Key Words. Epidermis • Sebaceous glands • Cell differentiation • Myc oncogene • β-catenin

Correspondence: Fiona M. Watt, MA, D.Phil., CR-UK Cambridge Research Institute, La Ka Shing Centre, Robinson Way, Cambridge CB1 ORE, United Kingdom. Telephone: +44 1223 404400; Fax: +44 1223 404573; e-mail: fiona.watt{at}cancer.org.uk

Received August 10, 2007; accepted for publication February 12, 2008.
First published online in STEM CELLS EXPRESS   February 28, 2008.



The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of β-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and β-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and β-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation.

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