Submitted on February 20, 2006
Accepted on June 16, 2006
TRANSCRIPTIONAL PROFILING OF EPIDERMAL DIFFERENTIATION
Nada Radoja1, Alix Gazel1, Tomohiro Banno2, Shoichiro Yano3, and Miroslav Blumenberg4*
1 Department of Dermatology, New York University School of Medicine, New York, New York, United States
2 Dermatology Department, Institute of Clinical Medicine, Tsukuba U., Tsukuba, Japan
3 Dermatology, New York University School of Medicine, New York, New York, United States
4 Department of Dermatology, New York University School of Medicine, New York, New York, United States; Department of Biochemistry, New York University School of Medicine, New York, New York, United States; NYU Cancer Institute, New York University School of Medicine, New York, New York, United States
* To whom correspondence should be addressed. E-mail: blumem01{at}med.nyu.edu.
In epidermal differentiation basal keratinocytes detach from the basement membrane, stop proliferating, and express a new set of structural proteins and enzymes, which results in an impermeable protein/lipid barrier that protects us. To define the transcriptional changes essential for this process, we purified large quantities of basal and suprabasal cells from human epidermis, using the expression of 
4 integrin as the discriminating factor. The expected expression differences in cytoskeletal, cell cycle and adhesion genes confirmed the effective separation of the cell populations. Using DNA microarray chips, we comprehensively identify the differences in genes expressed in basal and differentiating layers of the epidermis, including the ECM components produced by the basal cells, the proteases in both the basal and suprabasal cells, and the lipid and steroid metabolism enzymes in suprabasal cells responsible for the permeability barrier. We identified the signaling pathways specific for the two populations, and found two previously unknown paracrine and one juxtacrine signaling pathway operating between the basal and suprabasal cells. Furthermore, using specific expression signatures, we identified a new set of late differentiation markers and mapped their chromosomal loci, as well as a new set of melanocyte-specific markers. The data represent a quantum jump in understanding the mechanisms of epidermal differentiation.
