FluxSprout: Single-cell metabolic modeling of vascular sprouting in zebrafish

FluxSprout reconstructed zebrafish sprouting-angiogenesis metabolic network ensembles from 10,090 single cells, revealing biosynthetic capacity differences between sprouting and established vessels.

• Why it matters: Genome-scale metabolic modeling struggles with uncertainty from network annotations, thermodynamic feasibility, transcriptome-to-flux inference, and target specificity in heterogeneous systems.
• What they did: The framework integrates single-cell RNA-seq with Zebrafish-GEM, using stoichiometric auditing, loop auditing, cell-cycle-controlled testing, and ensemble specificity screening across 14 endothelial and hemogenic states.
• The result: It found that 19.5% of reactions can carry thermodynamically infeasible loop flux and that sprouting vessels show higher predicted growth capacity at both constraint strengths, with serine and nucleotide synthesis in fixed proportion.