Embryonic skin cells committed at an early age

Surprising results from a new research study demonstrate that the embryonic cells destined to become skin have an intrinsically high commitment to irreversible differentiation and are not, as was previously thought, a stem cell-like population with a high potential for growth. The study, published in the April edition of Developmental Cell, reveals the specific molecular mechanisms that drive the unexpected early differentiation of mouse embryonic skin cells and raises several interesting questions about how these cells might respond to genetic or environmental insults.

Little is known about the embryonic development of skin cells, called keratinocytes, in part because they are notoriously difficult to isolate and grow in the laboratory. Despite the absence of specific studies, popular belief held that embryonic keratinocytes are likely to share properties with stem cells and have a high potential for growth and expansion. To better understand the biology of embryonic skin cells, Dr. G. Paolo Dotto from Massachusetts General Hospital and Harvard Medical School and colleagues isolated pure keratinocyte populations from mouse embryos. The researchers found that the embryonic keratinocytes commit to becoming skin cells, or terminally differentiate, much prompter than cells after birth. The researchers went on to show that Notch signaling molecules, known to play a critical role in the determination of cell fate, account in part for this hastened differentiation.

The authors conclude that embryonic skin cells have a higher commitment to differentiation than cells at more mature stages and suggest that this characteristic may apply to other epithelial tissues as well. According to Dr. Dotto, "This has important implications for the possible utilization of embryonic versus newborn or adult tissues as enriched sources of stem cell populations for cell replacement purposes. The intrinsically high commitment to differentiation is also likely to have important consequences for susceptibility to environmental and/or toxic agents and cancer development. Cell populations that terminally differentiate at a fast rate likely provide a smaller target size than cells turning over at a slower rate. Conversely, more deleterious and uncontrolled effects could result from loss of normal growth/ differentiation mechanisms in cells that would be otherwise programmed to differentiate at an accelerated rate."

Ryuhei Okuyama, Bach-Cuc Nguyen, Claudio Talora, Eisaku Ogawa, Alice Tommasi di Vignano, Maria Lioumi, Giovanna Chiorino, Hachiro Tagami, Minna Woo, and G. Paolo Dotto: "High Commitment of Embryonic Keratinocytes to Terminal Differentiation through a Notch1-caspase 3 Regulatory Mechanism"

Published in Developmental Cell, Volume 6, Number 4, April 2004, page 551-562.

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