A method that enables gene expression analysis directly within tissue samples by sequencing short fragments of RNA is reported online this week in Nature Methods. This method can also be used to detect specific gene mutations in cells within body samples.
Currently available technologies for RNA sequencing use RNA transcripts extracted from cells, thus, gene expression data cannot be easily connected to information about the cells’ spatial organization within the tissue.
Mats Nilsson, Carolina Wahlby and their colleagues developed methods for in situ-that is, within the tissue-analysis of four-base-pair fragments of mRNA molecules. The authors used the method to detect the gene HER2 in biopsied breast cancer tissue, which helped them to distinguish cancerous from noncancerous tissue in the samples. Future development of the method will be needed to increase the sequencing length of the RNA samples but the authors show that four bases of sequence is enough to detect expression of individual genes in different cells within intact breast cancer tissue samples. This approach can help reveal genetic differences across a tissue and may advance our understanding of the genetic programs that become activated when a tissue becomes malignant.