We report the single-cell transcriptional profiling of sea urchin primary mesenchyme cells isolated from embryos treated with DMSO or with 5-lox activating protein (FLAP) inhibitor MK-886. We find that inhibition of LOX activity with MK-886 prior to PMC isolation induces shifts in gene expression within the PMC population. We further demonstrate that control PMCs cluster into four transcriptionally-defined subsets, and MK-886-treated PMCs cluster into five distinct subsets. These data highlight novel transcriptional paradigms in the diversification of PMCs, and the requirement of ectodermal LOX activity for proper PMC transcriptional diversification. Overall design: Examination of sea urchin primary mesenchyme cell transcriptional diversity and its regulation by ectodermally-expressed 5-lipoxygenase