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New biomarker evaluates iPSC viability.

LONDON, U.K., January 29, 2016 -- A research team here has found a way to assess the viability of induced pluripotent stem cells (iPSCs).

The University College London discovery may offer a new way to fast-track screening methods used in stem cell research.

iPSCs are derived from cells, usually taken from skin or blood, that have been genetically reprogrammed to revert back to an embryonic-like state so they can differentiate into any cell type in the body.

iPSC technology is an important platform for the study of human diseases in the laboratory: it offers the potential to develop transformative cell replacement therapies.

Not all iPSCs offer the same differentiation capacity, however, and some cell lines are markedly defective.

When generating iPSCs it is clearly beneficial to identify "good" and "bad" cell lines." Good cell lines offer optimal differentiation capacity and are therefore the most useful for research. However establishing the quality of these cell lines using traditional ways of assessment is costly and timeconsuming. The researchers were looking for a way to expedite this process. Part of the solution lies in using DNA methylation as a biomarker for differentiation capacity.

DNA methylation is a physical modification to the genetic material (DNA) of a cell, which can alter the behavior of that cell. In this study, the team looked for a particular type of methylation that only occurs in stem cells, known as non-CG methylation, to see if they could identify a link between non-CG methylation and differentiation capacity of iPSCs.

The role of a pluripotent stem cell is to generate all three germ layers: mesoderm, endoderm and ectoderm. These germ layers then develop into all cells of the body. For this study, researchers focused specifically on a pluripotent stem cell's ability to differentiate into the endodermal lineage for organs such as liver, pancreas and thyroid gland. The data showed a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages.

The researchers in fact found an epigenetic biomarker that can help distinguish iPSCs that have a diminished capacity for differentiation. This discovery can be used to reduce costly and time-consuming analysis methods, while simultaneously offering improvements in large-scale assessment of iPSC lines for clinical and therapeutic applications.

The discovery might be used in the short-term as an efficient analysis method of cell lines for research purposes. But it might also be used as a starting point for discovering the developmental processes associated with methylation patterns in iPSCs.

In time, these principles could impact understanding of cancer cell behavior and form a solid base for regenerative medicine strategies.

Citation: Lee M. Butcher et al., "Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells," Nature Communications, 2016; 7: 10458 DOI: 10.1038/ncomms10458

Abstract: http://goo.gl/EtcyYE

Contact: Stephan Beck, s.beck@ucl.ac.uk

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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Research News
Geographic Code:4EUUK
Date:Feb 1, 2016
Words:473
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