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. 2024 Mar 8;20(4):374–402. doi: 10.1038/s44320-024-00024-x

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© The Author(s) 2024

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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(A) Network connects major Reactome pathway clusters (numbered nodes). Colored bars inside each node present pathway cluster enrichment for CDm and ER-agonist-treated HFDm compared to HFDm (normalized enrichment score, NES). Edges connect positively-correlated (green) or negatively-correlated (black) nodes based on NES profiles. (B) UMAP space-projected enrichment plots highlight liver cell types with enhanced signal for the gene sets (defined in Fig. 2B). Hepatocyte nuclear fraction (snRNA-seq) is labeled. (C) Spatial transcriptomics maps show liver zonation patters of the gene sets (defined in Fig. 2B). (D) Bubble plots display activity scores of altered pathway clusters (A) across all liver cell types in control (left), HFD (middle) male mice and their differences (right). Color-code and circle diameter for enrichment score: low (yellow, narrow), high (black, wide). Arrows and enrichment change indicate higher abundance in control (red) and HFD (blue) mice.