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Skin cells switch between two modes for wound healing

Primary human keratinocytes appear able to switch back and forth between two reproductive modes, changing from a balanced mode where the rate of new cell production is just enough to keep up with routine cell death to an expanding mode where production outstrips attrition, aiding in wound closure, researchers report online in Nature Cell Biology (Dec. 7, 2015).

Using high-resolution cameras to observe more than 3,000 human skin cells dividing in culture, researchers from the Wellcome Trust Sanger Institute and MRC Cancer Unit at the University of Cambridge in England observed that the cells would switch back and forth between the modes based on certain stimuli.

They found that in the balanced mode, when the skin cells divided there was a 50% chance that the daughter cells would go on to themselves divide, and a 50% chance they would migrate—–which in human skin would bring them to the surface to eventually be shed. However, when the investigators scratched the sheet of human cells in their colony, cells adjacent to the wound switched modes and were nine times as likely to produce daughter cells that would themselves reproduce. Once the rapidly proliferating cells had closed the wound, they reverted to balanced reproduction.

"This research demonstrates that dividing human skin cells can switch their behaviour between these two modes of maintenance or repair, challenging the longstanding view that skin renewal and healing relies on a special population of stem cells," says Dr. Phil Jones, senior group leader at the institute and senior author of the study, in a press release.

As part of the study, researchers inhibited the cell signalling protein ROCK2 kinase, which they found prevented cells in expanding mode returning to the balanced mode. They write that this indicates that cell signalling was required to switch modes. Gene expression was also observed to be different between groups of cells exhibiting the two different reproductive behaviours.

"These findings have great implications for understanding cancer, where cells have too many dividing daughters,” Dr. Jones says in the release. “Mutations could change the rules of the game and load the dice in favour of dividing cells, leading to cancer."

"The knowledge that all dividing skin cells are the same but can switch their behaviour will help us understand how DNA changes associated with cancer alter cell behaviour,” said Dr. Jones.

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