Fig. 4: Multi-cell population modeling predicts metabolic activity of midbrain organoids.

a Metabolic modeling workflow (scFASTCORMICS, see methods). b Schematic overview of reconstructed model (per one condition). c Model similarity. Jaccard similarity coefficient based on reaction presence calculated for each pair of multi-cell population models, ranging from 0 (dissimilar) to 1 (equal). d Predicted medium uptake and secretion rates of midbrain organoids for key metabolites. Positive values [a.u.] indicate uptake of the respective metabolite and negative values [a.u.] indicate secretion. e Predicted lactate inter-cellular exchange between different cell types. Negative values [a.u.] indicate production of the respective metabolite and positive values [a.u.] indicate uptake (or secretion to the medium). f Expression of SLC16A7 in dopaminergic neurons of midbrain organoids. Dot size represents the cell percentage expressing the gene, colour represents the scaled average expression. g FluxSum estimates show the metabolic dependence of the midbrain organoid conditions in each energy pathway. Estimates are done by the sum of relevant metabolites (see Supplementary Table S5) within the respective pathway. TCA- tricarboxylic acid cycle; OXPHOS- oxidative phosphorylation; FAO- fatty acid oxidation.