Abstract

In recent years, macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; however, it remains unclear whether macrophages retain any persistent memory of past polarization states which may then impact their future repolarization to new states. Here, we perform deep transcriptomic profling at high temporal resolution as macrophages are polarized with cytokines that drive them into “M1” and “M2” molecular states. We fnd through trajectory analysis of their global transcriptomic profles that macrophages which are frst polarized to M1 or M2 and then subsequently repolarized demonstrate little to no memory of their polarization history. We observe complete repolarization both from M1 to M2 and vice versa, and we fnd that macrophage transcriptional phenotypes are defned by the current cell microenvironment, rather than an amalgamation of past and present states.