BioWorld International Correspondent

PARIS - French researchers identified the genetic markers that characterize stages in the differentiation of epidermal cells, saying it could result in a better understanding of the pathologies linked to cell differentiation and facilitate the identification and use of cells as therapies.

The research was carried out at the keratinocyte genomics and radiobiology unit of the French Atomic Energy Commission’s functional genomics laboratory in Evry.

It points out that the epidermis, which is composed mostly of keratinocytes, is in constant renewal, enabling the organism to resist the many onslaughts of its environment (variations in temperature, the sun, pathogenic microorganisms and so on). The epidermis regenerates thanks to its base of keratinocyte stem cells capable of constantly multiplying. At each division, those newborn keratinocytes produce two distinct cells: a new stem cell and another cell that starts to proliferate and then is transformed into a differentiated cell as it migrates toward the epidermis’ surface.

Researcher Gilles Lema tre explained the team’s approach.

“We sought to identify the molecular and cellular mechanisms that govern the differentiation of keratinocytes,” he said. “To do that, we combined a study of the genes activated in the cells [analyzing the transcriptome using DNA chips] with a study of the proteins they produce [analyzing the proteome through electrophoresis and spectrometry]. That enabled us to produce expression profiles of a very large number of genes for each stage of keratinocyte differentiation.”

The researchers thus were able to detect the activation and arrest of major metabolic pathways during the differentiation process. In particular, they succeeded for the first time in highlighting the decrease in glycolysis (the glucose uptake of cells) during the differentiation process. They also found that some genes thought to be specific to other types of cell were expressed in keratinocyte differentiation. And by comparing the different expression profiles, the researchers identified genes that were specifically activated at each stage of keratinocyte differentiation.

The head of the research team, Gilles Waksman, said that “by using these characteristic profiles as markers, we will be able to isolate and study each cell population separately, especially the stem cells that are the target of gene therapy and the instruments of cell therapy. That will enable us also to refine our knowledge of the keratinocyte differentiation process and better understand the physiopathological mechanisms involved in, for example, psoriasis, a disease that is characterized in effect by a hyperproliferation of keratinocytes.”

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