Transcriptional profiling of epidermal differentiation.
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 beta4 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.
Radoja
Nada
N
Department of Dermatology, New York University School of Medicine, New York, New York, USA.
Gazel
Alix
A
Banno
Tomohiro
T
Yano
Shoichiro
S
Blumenberg
Miroslav
M
D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D010447:Peptide Hydrolases