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. 2022 Oct 30;13:6499. doi: 10.1038/s41467-022-34241-5

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — a, c Schematic representation of the multi-level approach to study the effect of Fb on Mφ (a, b, e) and of Mφ on Fb (c, d, f) in a tissue-like setting with different metabolic and immune conditions.1st level compares cocultivated cells to single cultivated cells in four different conditions: in normoxic and resting (comparison A_M/A_F in pink), in hypoxic and resting (B_M/B_F in blue), in normoxic and inflamed (C_M/C_F in green), in hypoxic and inflamed (D_M/D_F in yellow). 2nd level (double arrows) compares normoxic to hypoxic environments (AvsB and CvsD) and 3rd level (triple arrows) compares resting to proinflammatory conditions [(A+B)vs(C+D)]. b, d Venn diagrams show the distribution of DEGs in each 1st level comparison in Mφ (b) and Fb (d). e, f Pathways enrichment analysis in Mφ (e) and Fb (f) comparisons. Columns represent 1st level of comparisons (A-B-C-D), rows report pathways significantly modulated (|z-score | ≥ 2) in at least one comparison. Color intensity bar indicates the level of positive (in red) or negative (in blue) enrichment; dots appear only when pathways are significantly enriched; gray indicates no modulation. See also Fig. S6. g Schematic representation of cellular changes in the key condition which feeds assumptions B and C in the mathematical model. Source data of heatmaps e, f are provided as a Source Data file.