新基因定序方法可对细胞更好地分析

Only by viewing a Seurat painting at close range can you appreciate the hidden complexities¹ of pointillism（点描绘法） -- small, distinct dots of pure color applied² in patterns to form an image from a distance. Similarly, biologists and geneticists have long sought to analyze⁴ profiles of genes⁵ at the single cell level but technology limitations have only allowed a view from afar until now. Research published in the July 22 issue of Nature Biotechnology, shows for the first time that a novel genomic sequencing method called Smart-Seq can help scientists conduct in-depth analyses of clinically relevant single cells. Smart-Seq has many possible applications, including helping⁶ scientists to better understand the complexities of tumor⁷ development. This is vitally important as many clinically important cells exist only in small numbers and require single cell analysis. The study was conducted by a team of researchers from the Ludwig Institute for Cancer Research, the Karolinska Institutet in Sweden, the University of California, San Diego and Illumina Inc.

 

"While our results are preliminary, we showed that it is possible to do studies of individual, clinically relevant cells," says biomedical scientist Rickard Sandberg, researcher at the Ludwig Institute for Cancer Research and principal investigator⁸ at the Department of Cell and Molecular⁹ Biology, Karolinska Institutet. "Cancer researchers around the world will now be able to analyze these cells more systematically¹⁰ to enable them to produce better methods of diagnosis¹¹ and therapy in the future."

 

Previous research showed that it is common for one gene³ to give rise to several forms of the same protein through different cut-and-paste configurations¹² of its raw copy. The phenomenon, known as splicing¹³（拼接） , means that cells from the same tissue are not so homogenous¹⁴（同质的） as previously¹⁵ thought.

 

The research team has now taken its study a step further and 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 accurately¹⁶ describe and study differences in gene expression between individual cells from the same tissue.

 

"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 sufficiently¹⁷ sensitive and robust¹⁸ method," says Dr. Sandberg. "The method has several areas of applications including cancer research where it can be used to study which cell types form cancer tumors in individual patients."

 

In the study, scientists studied tumor cells in the blood system of a patient with recurring¹⁹ malignant²⁰ melanoma. Once they had identified the tumor cells in a regular blood test, the team used Smart-Seq to analyze their gene expression. By using this method, researchers could show that the tumor cells had activated²¹ many important membrane²²（细胞膜） proteins that are understood to be responsible for their ability to evade²³ the body's monitoring system and spread in the blood or lymph（淋巴） .

 

The study was conducted with the support of several funding bodies, including the European Research Council, the Swedish Research Council, the Foundation for Strategic Research, the Åke Wiberg Foundation and the National Institutes of Health (NIH).

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