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bioRxiv · 10.1101/2025.04.11.648323

Pseudo-time trajectory of single-cell lipidomics: Suggestion for experimental setup and computational analysis

Jost, P. J.·Weindl, D.·Wunderling, K.·Thiele, C.·Hasenauer, J.
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Abstract

Cellular heterogeneity is a fundamental facet of cell biology, influencing cellular signaling, metabolism, and gene regulation. Its accurate quantification requires measurements at the single-cell level. Most high-throughput single-cell technologies provide only a snapshot of cellular heterogeneity at a specific time point because the measurement is destructive. This limits our current ability to understand the dynamics of cellular behavior and quantify cell-specific parameters. We propose an experimental setup combined with a model-based analysis framework, enabling the extraction of longitudinal data from a single destructive measurement. Although broadly applicable, we focus on lipid metabolism, a domain where obtaining longitudinal single-cell data has remained elusive due to technical constraints. Our method leverages multiple labels whose measurements are linked to a shared dynamic. This allows the estimation of cell-specific parameters and the quantification of heterogeneity. This framework establishes a foundation for future investigations, providing a roadmap toward a deeper understanding of dynamic cellular processes.

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Jost, P. J., Weindl, D., Wunderling, K., Thiele, C., Hasenauer, J.. 2025-04-17. Pseudo-time trajectory of single-cell lipidomics: Suggestion for experimental setup and computational analysis. https://doi.org/10.1101/2025.04.11.648323

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