Study of 'sister' stem cells uncovers new cancer clue

Public release date: 26-Sep-2013 [ | E-mail | Share ]

Contact: Graham Shaw graham.shaw@icr.ac.uk 44-020-715-35380 Institute of Cancer Research

Scientists have used a brand new technique for examining individual stem cells to uncover dramatic differences in the gene expression levels which genes are turned 'up' or 'down' between apparently identical 'sister' pairs.

The research, published today (Thursday) in Stem Cell Reports, was conducted and funded by The Institute of Cancer Research, London. It provides the latest evidence that despite having identical DNA, sister stem cells can display considerable differences in their molecular characteristics.

The study showed that DNA methylation, a process that controls which genes are expressed in cells, plays an important role in generating non-genetic (or 'epigenetic') differences between sister cells.

DNA methylation could therefore be one of the reasons for the major molecular variation between different cancer cells in the same tumour and drugs to reduce methylation might help control variation and make cancers easier to treat.

In the new research, scientists at The Institute of Cancer Research (ICR) developed a novel micro-dissection technique to separate pairs of sister embryonic stem cells for single cell RNA analysis [1].

Using their new high-tech method, researchers separated and isolated mouse stem cells from their sister pairs and measured the behaviour of key genes known to be expressed in those cells. By comparing which of these genes were up or down regulated, they determined the levels of similarity between sister cells at the molecular level for the first time.

They found that under normal conditions, pairs of sister stem cells displayed considerable differences to each other, showing nearly as much diversity as two cells from different sister pairs.

The researchers then looked at cells grown in the presence of a chemical cocktail called 2i, which reverts cells back to their most primitive stem cell state where they can make identical copies of themselves. They found that the cells had reduced levels of two enzymes critical for DNA methylation and they produced more similar sister cells.

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Study of 'sister' stem cells uncovers new cancer clue