Trajectory analysis quantifies transcriptional plasticity during macrophage polarization

• Published in: Scientific reports Vol. 10; no. 1; p. 12273
• Main Authors: Liu, Serena X., Gustafson, Heather H., Jackson, Dana L., Pun, Suzie H., Trapnell, Cole
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.07.2020; Nature Publishing Group
• Subjects: 631/337; 631/337/2019; 631/80; Animals; Biomarkers; Bone marrow; Cell growth; Chromatin Assembly and Disassembly; Cytokines; Cytokines - genetics; Disease; Gene Expression Profiling - methods; Genes; Genomes; Genotype & phenotype; Humanities and Social Sciences; Humans; Macrophage Activation - genetics; Macrophage Activation - immunology; Macrophages; Macrophages - immunology; Macrophages - metabolism; Medical research; Mice; multidisciplinary; Phenotype; Phenotypes; Plasticity; Polarization; Science; Science (multidisciplinary); Transcription; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68766-w

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 profiling at high temporal resolution as macrophages are polarized with cytokines that drive them into “M1” and “M2” molecular states. We find through trajectory analysis of their global transcriptomic profiles that macrophages which are first 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 find that macrophage transcriptional phenotypes are defined by the current cell microenvironment, rather than an amalgamation of past and present states.