Wednesday, 5 June 2013

New biomarker helps scientists choose the right stem cells

According to a new study by researchers at the Boston Children's Hospital and the Duke University, stem cells expressing a gene called WNT3, are more prone to differentiate into cells of the endoderm lineage, like the ones of the pancreas, liver and bladder. This strongly suggests that other genes could be used as biomarkers, capable of predicting the differentiation potential of stem cell lines. If such markers do exist, stem cell research would become both easier and cheaper.

Human embryonic and induced pluripotent stem cells have the capacity to differentiate into all different kinds of cells and tissues. Still, not all share the same differentiation potential, which is the ability to develop into specific types of cells. Typically, most stem cells are inclined towards developing cells of one of the three tissue lineages:
  • Endoderm (e.g. liver, pancreas)
  • Ectoderm (e.g. cornea, nervous system, teeth). 
  • Mesoderm (e.g. cartilage, circulatory system, kidneys) 

This has a significant impact on stem cell research, as investigators must first test several stem cell lines, which is expensive and time consuming, before choosing the one that is most efficient at producing the cells they need. Instead, they would prefer to select the most appropriate stem cell line right away, without having to worry for differentiation experiments, explained Yi Zhang, one of the two chief authors.

"If you want to differentiate stem cells into pancreatic cells, for instance, you want to start with a line with a high differentiation potential for endoderm. It's like athletes and sports. Some are built for football, some for baseball, some for swimming. Every cell line has its own strengths, and the challenge is knowing what those strengths are." said Zhang.

The researchers discovered that WNT3 can be used as a marker for endoderm differentiation while Wei Jiang, the other chief-author, was working on pancreatic cell development.

"Wei was testing different lines to find ones that we could use to generate pancreatic beta cells. He noted the correlation between WNT3 expression and endoderm differentiation efficiency in the lines he was testing and suggested that it might work well as a biomarker." explained Zhang.

Next, the duo collaborated with researchers from the Duke University and found that WNT3 can be used to predict the differentiation potential of human embryonic stem cells (hESCs). Furthermore, they discovered that by increasing or decreasing WNT3 expression, they could make hESCs more or less likely to develop into endoderm.

Human embryonic stem cells

How WNT3 expression actually affects the endoderm differentiation potential is still unclear, and is something Zhang wants to further investigate. For now, he believes that other genes have the potential to be used as markers for selecting lines inclined towards mesoderm and ectoderm development.

"We would like to find other markers and develop a scoring system, there are many hESC and iPSC lines, and we need a simple way to tell which to use in order to produce particular cell types." said Zhang.

Jiang, W., Zhang, D., Bursac, N., & Zhang, Y. (2013). WNT3 Is a Biomarker Capable of Predicting the Definitive Endoderm Differentiation Potential of hESCs Stem Cell Reports, 1 (1), 46-52 DOI: 10.1016/j.stemcr.2013.03.003 

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