A new study that uses high-definition movies of live cells reveals that skin cells can flip between two modes of proliferation: an expanding mode that is suited to wound repair and a balanced mode that is suited to tissue maintenance.
The study, by the Wellcome Trust Sanger Institute in Cambridge and the University of Cambridge, both in the UK, is published in the journal Nature Cell Biology.
The researchers discovered that in the expanding mode, the next generation of cells contains higher numbers of dividing than non-dividing cells, and in the balanced mode, the next generation of cells contains equal numbers of dividing cells and non-dividing cells.
Also, the presence of a wound appears to trigger the flip from balanced mode – where growth and shedding of cells is balanced and suits maintenance of tissue – to expanding mode, where accelerated growth is needed to repair the wound.
Senior author Dr. Phil Jones, who heads a lab specializing in epidermal stem cells, says:
“This research demonstrates that dividing human skin cells can switch their behavior 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.”
He and his colleagues liken the flip between the two states to changing the rules in a game of dice. When a cell divides into two daughter cells, the daughter cells can be dividing or non-dividing.
There are three possible outcomes from a cell division: outcome one results in two dividing cells, outcome two results in one dividing and one non-dividing cell, and outcome three results in two non-dividing cells.
In terms of a dice game, these outcomes are the equivalent of rolling a one or a two for two dividing cells, a three or a four for one dividing and one non-dividing, and a five or a six for two non-dividing cells.
In the balanced game, the odds of rolling any number between one and six are the same, thus any one of the three cell division outcomes has a one in three chance, ensuring a 50:50 even split between dividing and non-dividing cells in the next generation.
But in the expanding game, the researchers found that the odds of producing dividing cells are nine times higher – like a game of dice where the dice are loaded to favor outcomes that ensure that the numbers of dividing cells in ensuing generations rapidly outnumber non-diving cells.
For the study, the team took live imaging movies of more than 3,000 human skin cells dividing in culture thousands of times. These showed that single skin cells expand exponentially in repair mode until they produce multi-layered sheets of cells, and then switch to balanced mode.
However, the researchers also note with interest that what they observed from the single-cell growth was only half the story, as co-author Dr. Joanna Fowler, of the Sanger Institute, explains:
“By scratching sheets of cells in the balanced mode and observing cells next to the scrape, we saw that they changed into wound healing mode until the scratch was closed again. The cells could switch backwards and forwards between the two states as required, proving that the behaviors were reversible.”
It is as though the skin cells can sense when neighboring cells are lost, and this causes them to flip from maintenance to repair mode, and when they are surrounded by cells again, they flip back to maintenance mode.
On further investigation, the team found the “switch” in the form of the cell signalling protein ROCK2 kinase. When they blocked the protein, it stopped cells in expanding or repair mode being able to flip back into balanced or maintenance mode.
And in further tests, they found differences in gene expression between populations of cells in repair and balanced states.
The team believes the study helps to understand how skin cell cultures expand, and it could lead to further improvements in wound healing in the clinic.
The findings could also be important for understanding cancer, where cells have too many dividing daughters, says Dr. Jones, as he explains:
“Mutations could change the rules of the game and load the dice in favor of dividing cells, leading to cancer. The knowledge that all dividing skin cells are the same but can switch their behavior will help us understand how DNA changes associated with cancer alter cell behavior.”
Meanwhile, Medical News Today recently learned about a color-changing Band-Aid that gives early warning of infection. Ground-breaking work by UK researchers has led to a wound dressing for burns that changes color in response to infection. The innovation could help in the global fight against antibiotic resistance, they said.