Methylation and Transcriptomic Profiling Reveals Short Term and Long Term Regulatory Responses in Polarized Macrophages [RNA-Seq]
Macrophage plasticity allows the adoption of distinct functional states in response to environmental  cues. While unique transcriptomic profiles define these states, focusing solely on transcription neglects  potential long-term effects. The investigation of epigenetic changes can be used to understand how  temporary stimuli can result in lasting effects. Moreover, epigenetic alterations play an important role  in the pathophysiology of macrophages, including phenomena related to the trained innate immunity,  which allow faster and more efficient inflammatory responses upon subsequent encounters with the  same pathogen. In this study, we used a multi-omics approach to elucidate the interplay between gene  expression and DNA-methylation, unravelling the long-term effects of diverse polarizing environments  on macrophage activity. We identified a common core set of genes that are differentially methylated  regardless of exposure suggesting a potential mechanism for rapid adaptation to various stimuli. These  conserved epigenetic modifications might represent a fundamental state that allows for flexible  responses to various environmental cues. Functional analysis revealed that processes requiring rapid  responses displayed transcriptomic regulation, whereas functions critical for long-term adaptations  exhibited co-regulation at both transcriptomic and epigenetic levels. Our study unveils a novel set of  genes critically linked to the long-term effects of macrophage polarization. This discovery underscores  the potential of epigenetics in elucidating how macrophages establish long-term memory and influence  health outcomes. Overall design: We studied how the macrophage polarization leads to long-term reprogramming. We did this by first turning monocytes into macrophages using a chemical trigger (phorbol 12-myristate 13-acetate), and then exposing them to various signaling molecules (LPS, INFgamma, IL13, IL14) at different time points.