Fig. 1: Basal cells permit SCLC subtype diversity.
From: Basal cell of origin resolves neuroendocrine–tuft lineage plasticity in cancer
a, Schematic of SCLC induction in RPM GEMMs with basal-specific Cre. b, RPM K5–Cre tumour haematoxylin and eosin (H&E): whole lobes (top) and tumour morphology (bottom). c, Immunohistochemistry for indicated proteins in RPM tumours from indicated Ad–Cre. K5–Cre mice pretreated with naphthalene injury. d, POU2F3+ tumours (H-score above 50) per lung per mouse (n indicated) by Ad–Cre. One-way analysis of variance (ANOVA) with post hoc Tukey’s P values shown. Error bars = mean ± s.e.m. e, H-score quantification of RPM tumours for indicated markers by Ad–Cre. Tumour number indicated; n = 4–18 mice per group. f, Schematic of RPM basal organoid and allograft generation. g, Bright-field images of RPM organoids pre- (wild type) and post-CMV–Cre (transformed). h, H&E of RPM allografts with classic (top) or variant (bottom) histology. i, scRNA-seq UMAP from wild type (n = 1) and RPM basal organoids (n = 2) and the resulting RPM allografts (n = 2 independent experiments) with basal versus NE cell signature enrichment. Cell number analysed per sample is indicated. j, Left, Leiden clusters in UMAP of downsampled RPM allografts (n = 2 independent experiments; n = 4,435 cells; Supplementary Table 1). Right, expression of indicated genes in UMAP (top) and by Leiden clusters (bottom). Red circle, Pou2f3 + cluster 20. k, UMAP in j annotated by SCLC fate. l–n, UMAP in j of NE score (l) and violin plots of NE score (l), NE/tuft/basal cell signatures (m) and ChIP–seq targets and YAP1 activity by SCLC fate (n) (Supplementary Table 2). o, Co-immunofluorescence for DAPI (nuclei) and indicated proteins in RPM allografts. Yellow arrows mark co-expressing cells. Violin plots show median and upper/lower quartiles. Unless otherwise noted, statistics are Kruskal–Wallis (KW) tests with post hoc uncorrected (e) or Bonferroni-corrected (l–n) Dunn’s pairwise comparisons. ****P < 2 × 10−16; NS, not significant (P > 0.05); other P values indicated. Scale bars: 1 mm (b, top), 50 μm (b, bottom, c,h), 10 μm (c, insets), 650 μm (g, left), 275 μm (g, right), 75 μm (o). Schematics in a and f were created using BioRender (https://biorender.com).
