Extended Data Fig. 4: Tip-like and stalk-like cells in TVM.
a-b. Visualization of trajectories inferred by Slingshot, VIA, and Monocle3 in tip-like (a) and stalk-like (b) cells, respectively. c. Boxplot showing the CytoTRACE scores among differentiation stages of tip-like (top) and stalk-like (bottom) cells (tip cells: SI, n = 9,063, SII, n = 13,390, SIII, n = 6,351; stalk cells: SI, n = 4,399, SII, n = 3,361, SIII, n = 5,517). d. Violin plots showing the HIF1A activity at transcription levels (top), AUCell score of target genes (middle), and DoRothEA activity (bottom). Error bar represents mean ± standard deviation. e. Violin plots showing the expression of staged markers. f. Representative mIHC of APLN+ TipSI markers in LUAD from n = 10 independent biological replicates, GBM from n = 11 independent biological replicates, and HCC from n = 10 independent biological replicates. Scale bar, 50 µm. g. SOM (50 × 50 grid) constructed from single-cell transcriptomes of tip-like and stalk-like cells showing scaled metagene expression. Black lines demarcate eight overexpressed metagene-signatures comprising 971 overexpressed genes. h. Function enrichment of overexpressed metagenes interrogated by SOM, resulting in ten TAPFs. P-values are calculated based on the cumulative hypergeometric distribution. i-j. Tip-to-stalk communications in angiogenic stages. Heatmap showing the activities of top 20 ligands (i). Dot plot showing the stage-related LR pairs (j), sized by the pseudobulk Spearman’s correlation P-value and coloured by the interaction potential predicted using NicheNet. k. Violin plot showing the expression levels of genes associated with TAPFs. For boxplots, centre line represents median, box limits indicate upper and lower quartiles, and whiskers extend 1.5 times the interquartile range. Statistical analysis was performed using Kruskal-Wallis test (c).
