Since 2007, Linnarsson has pursued single-cell biology with the ultimate aim to discover the complete lineage tree of the developing human nervous system. To achieve this goal, his group pioneered single-cell RNA sequencing, RNA single-molecule FISH, and advanced computational methods.

In 2011, Linnarsson showed that cell types could be directly discovered and distinguished de novo, by unbiased sampling and sequencing of large numbers of single cells, without use of previously known markers. In his pioneering 2011 Genome Research paper, he laid the conceptual foundation for the single-cell genomics field, envisioning “the future use of very large-scale single-cell transcriptional profiling to build a detailed map of naturally occurring cell types, which would give unprecedented access to the genetic machinery active in each type of cell at each stage of development.”