Title:	Decoding macrophage plasticity
DNr:	Berzelius-2025-427
Project Type:	LiU Berzelius
Principal Investigator:	Emma Lundberg <emma.lundberg@scilifelab.se>
Affiliation:	Kungliga Tekniska högskolan
Duration:	2025-12-15 – 2026-07-01
Classification:	10610
Keywords:

Abstract

Macrophages are infiltrating immune cells that play a central role in innate immunity but also in normal tissue development, maintenance of homeostasis, and repair of damaged tissue. A key feature of macrophages is their plasticity, the ability to adopt pro- or anti-inflammatory phenotypes in response to environmental cues. To date, most studies investigating macrophage plasticity rely heavily on single-cell transcriptomics or mass spectrometry (MS)-based proteomics. While these technologies provide valuable insights into gene and protein expression, they offer limited spatial context regarding subcellular protein localization or morphological features. In this project, we propose an alternative and complementary approach to investigate macrophage plasticity. By leveraging a high-throughput, multiplexed imaging technique targeting morphological markers combined with ~500 macrophage specific markers, we aim to visualize and quantify the spatial distribution of cellular structures and proteins. Specifically, we applied our methodology to primary blood monocyte-derived macrophages stimulated with a range of cytokines to induce diverse polarization states. To analyze this complex imaging dataset, we will use our in-house machine learning model, SubCell, to extract and interpret subcellular morphological features but also predict protein localization patterns across macrophage states. Ultimately, we believe that analyzing changes in protein distribution at the subcellular level, in conjunction with detailed morphological profiling, will provide a novel lens through which to study macrophage plasticity and future integrative approaches in cell biology.