Single-Cell Multiomics of Macrophage Polarization in Inflammatory Microenvironments
DOI:
https://doi.org/10.66238/fsrma79Keywords:
Macrophage Polarization, Single-Cell Multiomics, Transcriptomics, Inflammatory MicroenvironmentAbstract
Macrophages are highly plastic innate immune cells that adapt their functional phenotypes in response to environmental cues, a process traditionally conceptualized as polarization. However, the binary classification of classically activated and alternatively activated macrophages fails to capture the immense phenotypic diversity observed in vivo, particularly within complex inflammatory microenvironments. Recent advances in single-cell multiomics technologies have revolutionized our understanding of macrophage heterogeneity by enabling the simultaneous profiling of the transcriptome, epigenome, and surface proteome at single-cell resolution. This paper provides a comprehensive overview of how single-cell multiomics has redefined macrophage polarization from a distinct set of binary states to a multi-dimensional continuum of activation trajectories. We explore the limitations of conventional bulk sequencing approaches and discuss the fundamental principles of multiomic integration. Furthermore, we examine the computational frameworks required to delineate complex cellular trajectories and assess the regulatory gene networks governing macrophage plasticity in various pathological contexts, including the tumor microenvironment and chronic autoimmune diseases. By dissecting the epigenetic priming and transcriptomic execution of macrophage activation, this paper highlights the pivotal role of single-cell multiomics in identifying novel therapeutic targets for immune modulation. Ultimately, these high-resolution analytical frameworks pave the way for precision medicine strategies aimed at reprogramming dysregulated macrophage populations in severe inflammatory disorders.
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