Trajectory analysis quantifies transcriptional plasticity during macrophage polarization

Serena X Liu,Suzie H Pun,Heather H Gustafson,Dana L Jackson,Cole Trapnell

doi:10.1038/s41598-020-68766-w

Serena X Liu, Suzie H Pun + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-68766-w

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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 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.

Highlights

IntroductionMacrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; it remains unclear whether macrophages retain any persistent memory of past polarization states which may impact their future repolarization to new states
In recent years, macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; it remains unclear whether macrophages retain any persistent memory of past polarization states which may impact their future repolarization to new states
While cellular plasticity is perhaps best known as a canonical feature of embryonic differentiation in early development, it is crucial for enabling differentiated cells to respond dynamically to changing microenvironments, as in the case of immune cells redirecting their function in response to different extracellular s ignals[1]

Summary

Introduction

Macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; it remains unclear whether macrophages retain any persistent memory of past polarization states which may impact their future repolarization to new states. Macrophage dysfunction has been implicated in a wide array of diseases, including a sthma6–8, obesity9–12, cancer[13,14,15,16,17], and a therosclerosis[14,18,19] In many of these cases, macrophages are thought to play a key role in disease pathogenesis and are considered a promising therapeutic target. While macrophage plasticity is well-established, it remains unclear the extent to which macrophages retain any memory of past phenotypic states and whether a cell’s history might impact its future response to Scientific Reports | (2020) 10:12273

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