This study investigates the heterogeneity in the response of bone marrow-derived dendritic cells (BMDCs) to lipopolysaccharide (LPS) using single-cell RNA-Seq. The researchers found extensive and previously unobserved bimodal variation in mRNA abundance and splicing patterns, validated by RNA-FISH for select transcripts. Hundreds of key immune genes showed bimodal expression across cells, even for genes highly expressed at the population average. Splicing patterns also demonstrated significant heterogeneity between cells. Some bimodality was attributed to distinct maturity states of BMDCs, while other portions reflected differences in the usage of key regulatory circuits. The study highlights the power of single-cell genomics in uncovering functional diversity between cells and deciphering cell states and circuits.This study investigates the heterogeneity in the response of bone marrow-derived dendritic cells (BMDCs) to lipopolysaccharide (LPS) using single-cell RNA-Seq. The researchers found extensive and previously unobserved bimodal variation in mRNA abundance and splicing patterns, validated by RNA-FISH for select transcripts. Hundreds of key immune genes showed bimodal expression across cells, even for genes highly expressed at the population average. Splicing patterns also demonstrated significant heterogeneity between cells. Some bimodality was attributed to distinct maturity states of BMDCs, while other portions reflected differences in the usage of key regulatory circuits. The study highlights the power of single-cell genomics in uncovering functional diversity between cells and deciphering cell states and circuits.