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. 2022 Nov 25;54(11):2060–2076. doi: 10.1038/s12276-022-00896-9

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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. 7 — a ST analysis was used to subregionalize the cancer region in the HE-stained cancer region (upper panel: AIS, TD8; middle panel: MIA, TD3; lower panel: IAC, TD1). b Venn diagram showing overlapping genes specific for cell type of scRNA-seq data and tissue region of ST data from among 33,538 genes. c The hypergeometric distribution method was applied to match the four cancer subtypes identified by scRNA-seq data with the cancer location-specific genes identified by ST data. d Heatmap of GSVA results showing differences in the pathway activity in different spatial cancer subregions (left panel: AIS, TD8; middle panel: MIA, TD3; right panel: IAC, TD1). e GSVA data showing differences in the expression of genes downstream of the TGF-β pathway in cancer cells with different spatial distributions. f IF validated differences in the activity of cancer cells with different spatial distributions (PCNA expression). g Hypothetical models illustrating that the UBE2C + cancer cell subcluster increases and recruits Tregs, repels NK cells and mast cells, and promotes the invasive progression of LUAD from AIS to IAC.