Speaker
Description
Macrophages are innate immune cells with a wide range of functional capacities \cite{Wu}. They have been broadly classified into M1 or M2 phenotypes based on environmental signals. Due to variation in such regulatory cues, these macrophages are thought to also show states that are intermediate within a spectrum that has M1 and M2 at its two extremes \cite{Ka}. However, across all these studies, characterization for hybrid macrophages is not consistent due to overlapping macrophage markers. How hybrid macrophages arise, how stable these states are, how easy is it for them to transition from, or to M0, M1, or M2 states, and how is their stability reinforced or attenuated by the distinct secretory states remains poorly understood. To address these set of problems, we define the hybrid macrophage phenotype based on gene regulatory network (GRN) information at intracellular scale. Our findings reveal a 'teams' structure as an emergent property of the macrophage GRN. Perturbation analysis was done with M1 and M2 as initial states and as two different cases. In one node perturbation, the system is unable to switch its phenotype in either case, but in some two and three-node combinations, the system can switch to hybrid phenotype. Furthermore, overexpression analysis was done, where STAT3 and STAT1 combination was specifically observed to give rise to the most hybrid populations. The phenotypic distribution obtained from the Boolean framework was then validated using RAndom CIrcuit PErturbation (RACIPE). The distribution of steady state in overexpression analysis using RACIPE was consistent with the Boolean framework, making the distribution of steady states a robust dynamical property of the network.
Bibliography
@ARTICLE{Wu,
title = "The {M1/M2} spectrum and plasticity of malignant pleural
effusion-macrophage in advanced lung cancer",
author = "Wu, Ming-Fang and Lin, Chih-An and Yuan, Tzu-Hang and Yeh,
Hsiang-Yuan and Su, Sheng-Fang and Guo, Chin-Lin and Chang,
Gee-Chen and Li, Ker-Chau and Ho, Chao-Chi and Chen, Huei-Wen",
journal = "Cancer Immunol. Immunother.",
publisher = "Springer Science and Business Media LLC",
volume = 70,
number = 5,
pages = "1435--1450",
month = may,
year = 2021,
}
@ARTICLE{Ka,
title = "Tumour-educated macrophages display a mixed polarisation and
enhance pancreatic cancer cell invasion",
author = "Karnevi, Emelie and Andersson, Roland and Rosendahl, Ann H",
journal = "Immunol. Cell Biol.",
publisher = "Wiley",
volume = 92,
number = 6,
pages = "543--552",
month = jul,
year = 2014,
}
