Grindberg, R.V. et al. Proc. Natl. Acad. Sci. USA 110, 19802–19807 (2013).

High-throughput RNA sequencing can be used to measure gene expression in single cells, but some cells are difficult to isolate because they are delicate or embedded in complex tissues. As an alternative, Grindberg et al. show that it is possible to access the transcriptome of single cells by sequencing RNA from their nuclei. Nuclei are generally easier to isolate than whole cells and do not require heating, which is associated with enzymatic dissociation of whole cells, thus reducing the chance of disturbing the transcriptional state of the cell. The researchers applied a common single-cell RNA sequencing protocol to nuclei from single mouse hippocampal neurons and demonstrated that the sequencing results were very similar to those for whole neuronal progenitor cells, despite the fact that the nucleus can contain 10–100-fold less mRNA.