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Posted: Jul 25, 2012

Getting intimate: scientists get closer to individual cells thanks to smarter analysis

(Nanowerk News) Sometimes you need to get up close and personal to really see something clearly, and in this vein biologists and geneticists have long dreamt of being able to analyse profiles of genes at the single cell level, but limitations of the available technology have meant they had to content themselves with viewing them from further away.
But now a research team from Sweden and the United States has shown that a novel genomic sequencing method called 'Smart-Seq' can help scientists conduct in-depth analyses of clinically relevant single cells.
Writing in the journal Nature Biotechnology ("Full-Length mRNA-Seq from single cell levels of RNA and individual circulating tumor cells"), the researchers present the potential applications of Smart-Seq, which include helping scientists better understand the complexities of tumour development.
The work was supported by the EU-funded project SINGLE-CELL GENOMICS ('Single-cell gene regulation in differentiation and pluripotency'), which was funded to the tune of EUR 1,654,383 by the European Research Council (ERC).
Study author Dr Rickard Sandberg from the Ludwig Institute for Cancer Research in Sweden comments: 'While our results are preliminary, we showed that it is possible to do studies of individual, clinically relevant cells. Cancer researchers around the world will now be able to analyse these cells more systematically to enable them to produce better methods of diagnosis and therapy in the future.'
Previous studies have shown that it is common for one gene to give rise to several forms of the same protein through different cut-and-paste configurations of its raw copy. The phenomenon is known as splicing and means that cells from the same tissue are not as homogenous as was previously thought.
This new study has taken things one step further and has developed a method for the complete mapping of the gene expression of individual cells. In showing which genes are active, it is now possible to accurately describe and study differences in gene expression among individual cells from the same tissue.
Dr Sandberg continues: 'Scientists have been waiting for a long time for such a method to come along, but technical limitations have made it difficult to produce a sufficiently sensitive and robust method. The method has several areas of applications including cancer research where it can be used to study which cell types form cancer tumours in individual patients.'
The team studied tumour cells in the blood system of a patient with recurring malignant melanoma. Once they had identified the tumour cells in a regular blood test, the team used Smart-Seq to analyse their gene expression. This method helped them show that the tumour cells had activated the important membrane proteins that are understood to be responsible for the tumour cells' ability to evade the body's monitoring system and spread in the blood or lymph.
The main aim of the SINGLE-CELL GENOMICS project, which runs until 2015, is to better understand gene regulation during in vivo differentiation and in pluripotent cells by studying single cells from murine preimplantation embryos, a model system with natural single cell resolution, and important biological and medical potential.
Source: Arizona State University
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