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New study highlights need for careful evaluation of stem cell gene regulation

11 May 2012
Human Embyronic Stem Cell Colony (courtesy of Dr Andrew Laslett)

A large international team of scientists, including CSIRO’s Dr Andrew Laslett, has shown that the way specific genes are regulated in human stem cells is affected by how the cells are grown in the laboratory. The findings have important implications for the use of stem cells to model disease-in-a-dish for certain conditions.

Human pluripotent stem cells can give rise to virtually every type of cell in the body. Because of this remarkable quality, these cells offer scientists a new way to better understand disease and screen for new drugs that may help those suffering from particular conditions. Of course this disease-in-a-dish approach relies on the cells behaving the same way in the laboratory as they do in the patient.

In a recent international study, researchers - including CSIRO’s Dr Andrew Laslett – explored how gene expression is controlled through epigenetic regulation in a large number of human pluripotent stem cell lines (over 200) and compared them to normal human tissue samples. They showed that amongst the lines examined there was variation in gene silencing through DNA methylation. DNA methylation is the molecular mechanism by which DNA is tagged so that a specific gene sequence, or small section of DNA, when tagged is not expressed (and by extension the protein coded for by that gene is then also not made by the cell).

While these changes appeared to be linked to culture conditions and may have implications for modelling of studying some diseases in the laboratory, normal control of gene expression during differentiation was also observed as noted by Stem Cell Sciences’ Professor Martin Pera.“The team examined hundreds of stem cell lines to evaluate how faithfully they reproduce epigenetic regulation during embryonic development. As observed previously, they were able to show that there were some abnormalities in X inactivation, the process whereby of the X chromosomes in female cells is shut off.  However, in general normal epigenetic controls came into operation as the stem cells turned into specialized cell types - an encouraging finding. “

Led by researchers at The Scripps Research Institute and the University of California (UC) San Diego, and recently published in the journal Cell Stem Cell, the study highlights the need to fully characterise the stem cells used in laboratory research and be aware of potential limitations. As co-author Dr Laslett commented, “These findings illustrate the importance of examining and understanding the baseline epigenetic information about the cells that researchers are seeking to use to create disease models”.

Dr Laslett also highlighted the need for a multinational and multi-institutional approach to such challenges stating that “conducting such an extensive analysis would not be impossible without this type of collaboration.”

Find out more:

Nazor et al (2012) Recurrent Variations in DNA Methylation in Human Pluripotent Stem Cells and Their Differentiated Derivatives. Cell Stem Cell 10(5):620-634. [subscription maybe required]

Study reveals dynamic changes in gene regulation in human stem cells [Press Release – Scripps Research Institute]

Questions arise about disease-in-a-dish model for some diseases [CIRM]

Scientists discover new type of dynamic change in human stem cells [News Medical]