Exploring heterogeneous cell population dynamics in different microenvironments by novel analytical strategy based on images

• Published in: NPJ systems biology and applications Vol. 10; no. 1; pp. 129 - 10
• Main Authors: Huang, Yihong, Zhou, Zidong, Liu, Tianqi, Tang, Shengnan, Xin, Xuegang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.11.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/553/2701; 631/80; Actin; Actin Cytoskeleton - metabolism; Annotations; Bioinformatics; Biology; Biomedical and Life Sciences; Cell culture; Cell Culture Techniques - methods; Cell Line; Cell Shape - physiology; Cell size; Cells; Cellular Microenvironment - physiology; Collagen; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Contractility; Cytoskeleton; Datasets; Hepatic Stellate Cells - metabolism; Humans; Image Processing, Computer-Assisted - methods; Labeling; Life Sciences; Machine learning; Microenvironments; Morphology; Stellate cells; Systems Biology; Trends
• ISSN: 2056-7189; 2056-7189
• DOI: 10.1038/s41540-024-00459-w

Understanding the dynamic states and transitions of heterogeneous cell populations is crucial for addressing fundamental biological questions. High-content imaging provides rich datasets, but it remains increasingly difficult to integrate and annotate high-dimensional and time-resolved datasets to profile heterogeneous cell population dynamics in different microenvironments. Using hepatic stellate cells (HSCs) LX-2 as model, we proposed a novel analytical strategy for image-based integration and annotation to profile dynamics of heterogeneous cell populations in 2D/3D microenvironments. High-dimensional features were extracted from extensive image datasets, and cellular states were identified based on feature profiles. Time-series clustering revealed distinct temporal patterns of cell shape and actin cytoskeleton reorganization. We found LX-2 showed more complex membrane dynamics and contractile systems with an M-shaped actin compactness trend in 3D culture, while they displayed rapid spreading in early 2D culture. This image-based integration and annotation strategy enhances our understanding of HSCs heterogeneity and dynamics in complex extracellular microenvironments.