Insights into the Identification of iPSC- and Monocyte-Derived Macrophage-Polarizing Compounds by AI-Fueled Cell Painting Analysis Tools

单核细胞 巨噬细胞 鉴定(生物学) 计算生物学 细胞生物学 细胞 化学 生物 免疫学 生物化学 植物 体外
作者
Johanna B. Brüggenthies,Jakob Dittmer,Eva M. Garrido-Martín,Igor Zingman,Ibrahim Tabet,Helga Bronner,Sarah Groetzner,Julia Sauer,Mozhgan Dehghan Harati,Rebekka Scharnowski,J.M.T. de Bakker,Katharina Riegger,Caroline Heinzelmann,Birgit Ast,Robert Ries,Sophie Fillon,Anna Bachmayr-Heyda,Kerstin Kitt,Marc A. Grundl,Ralf Heilker,Lina Humbeck,Michael Schuler,Bernd Weigle
出处
期刊:International Journal of Molecular Sciences [MDPI AG]
卷期号:25 (22): 12330-12330
标识
DOI:10.3390/ijms252212330
摘要

Macrophage polarization critically contributes to a multitude of human pathologies. Hence, modulating macrophage polarization is a promising approach with enormous therapeutic potential. Macrophages are characterized by a remarkable functional and phenotypic plasticity, with pro-inflammatory (M1) and anti-inflammatory (M2) states at the extremes of a multidimensional polarization spectrum. Cell morphology is a major indicator for macrophage activation, describing M1(-like) (rounded) and M2(-like) (elongated) states by different cell shapes. Here, we introduced cell painting of macrophages to better reflect their multifaceted plasticity and associated phenotypes beyond the rigid dichotomous M1/M2 classification. Using high-content imaging, we established deep learning- and feature-based cell painting image analysis tools to elucidate cellular fingerprints that inform about subtle phenotypes of human blood monocyte-derived and iPSC-derived macrophages that are characterized as screening surrogate. Moreover, we show that cell painting feature profiling is suitable for identifying inter-donor variance to describe the relevance of the morphology feature ‘cell roundness’ and dissect distinct macrophage polarization signatures after stimulation with known biological or small-molecule modulators of macrophage (re-)polarization. Our novel established AI-fueled cell painting analysis tools provide a resource for high-content-based drug screening and candidate profiling, which set the stage for identifying novel modulators for macrophage (re-)polarization in health and disease.
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