We detect 4000 more genes in single cells than single nuclei, but the majority of genes are detected equally well by both. Cytoplasm-enriched transcripts are missed by profiling single nuclei but include mostly house-keeping genes and pseudogenes and are not related to neuronal identity. Nucleus-enriched transcripts include protein-coding and non-coding genes that are more likely to be cell type markers than cytoplasmic transcripts. However, single cells do have somewhat better detection of cell type marker genes which resulted in slightly better cluster separation for two highly similar cell types. Therefore, as more nuclei and cells are profiled, it is possible that finer resolution splits may not be possible with nuclei.
However, there are many benefits to using single nuclei that may outweigh ultimate cell type resolution.