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. 2023 Mar 30;25:34. doi: 10.1186/s13058-023-01639-y

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© The Author(s) 2023

Open AccessThis 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Different dynamic evolutionary characteristics of tumor cells in HER2_low and HER2_neg TNBC. (A) Density of tumor cells along pseudotime in two TNBC groups. The vertical axis is the pseudotime process from bottom to top, the horizontal axis is the composition of cell clusters at different pseudotime state (displayed by TNBC groups). The main tumor clusters of the two groups have been annotated, diverging from early to late lineages 1,2, and 3, respectively. (B) The box plot shows the differentiation status of each tumor cell subcluster using CytoTRACE. Tumor clusters marked in blue and orange fonts are specific clusters of HER2_neg and HER2_low TNBC, respectively, and the clusters marked in green font are shared by the two TNBC groups. (C) Trajectory of the evolution of tumor cells predicted by monocle. The dashed arrows indicate the direction of evolution. (D) Three states of tumor evolution in all tumor cells. From State 1 to State 3 indicates that tumor cell evolution from early to late stages. (E) Heatmap indicates the gene expression signatures of the three evolutionary states. (F) Trajectory reconstructions of tumor cells in the HER2_low TNBC and (G) HER2_neg TNBC, respectively, revealing three branches including pre-branch, fate 1, and fate 2. (H) Heatmaps show upregulated or downregulated genes along with the two differentiation fates and the GO enrichment analysis in HER2_low and (I) HER2_neg TNBC groups, indicating active signature pathways for each branch in two groups. The abscissa is from the middle to the left and right sides (fate 1, fate 2), representing the tumor evolution process from early to late; the ordinate represents the gene, and each point represents the average expression of the specified gene in the pseudotime. Genes with similar expression patterns are clustered into one module