Extended Data Fig. 1: Lung cancer promotes changes in the chromatin state of BM myeloid progenitors.
From: Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours
a, Averaged heatmap for abundance of LT-HSCs, progenitors, and mature populations in bone marrow (BM) of KP tumor-bearing mice at different timepoints, normalized to tumor-naïve mice (left to right, n = 10,7,12,12). Pooled from two independent experiments. b, Granulocytic-monocytic colony forming units (CFU-GM) relative to erythroid blasts (BFU-E) after 8 days of incubation. n = 4 replicates. Pooled from two independent experiments. c, Longitudinal expansion of sorted GMPs from naïve and KP tumor-bearing mice. n = 3 replicates from one experiment. d, Number of Ly6Chi monocytes and Ly6Ghi neutrophils in blood of naïve and KP tumor-bearing mice at different time points, correlated with tumor burden. Data are individual data points with confidence intervals for linear regression (left to right, n = 5,7,12,12). Pooled from two independent experiments. e, Number of GMPs, cMoPs, and CD157+ Ly6Chi monocytes in BM, and number of Ly6Chi monocytes in blood of KP GEMM at 12 weeks post tumor initiation, compared to tumor-free mice. n = 3 mice per group, representative of two independent experiments. f, scRNA-seq heatmap of per-cell UMI counts across indicated myeloid cell subclusters in BM of tumor-bearing and naïve mice. Pooled over n = 3 mice per group. g, Gene ontology (GO) terms enriched in KP tumor-bearing mouse GMPs (left) and cMoPs (right) compared to naïve counterparts. Curated terms arranged by adjusted p-value (log q-value). h, Gene ontology (GO) terms enriched in PyMT tumor-bearing mouse GMPs compared to naïve counterparts from Gerber-Ferder et al.13 (left) and Hao et al. 2023 (right). Curated terms arranged by adjusted p-value (log q-value). i, exemplar scATAC-seq UMAP and heatmap of column-normalized gene scores across indicated myeloid cell subclusters in BM of tumor-bearing and naïve mice. Pooled over n = 3 mice per group. j, scATAC-seq heatmap of normalized transcription factor (TF) motif accessibility enrichment in marker peak regions of indicated myeloid cell states. Pooled from n = 3 mice per group. k, GREAT pathway terms enriched in indicated H3K4me3 regions from BM GMPs and Ly6Chi monocytes of KP tumor-bearing mice (Fig. 1f). Curated terms arranged by adjusted p-value (q-value). l–m, H3K4me1, H3K27ac, and H3K27me3 CUT&RUN signal clustering (l) and relative DORC scores for exemplar genes (m) in KP tumor-associated GMP relative to naïve GMP. n, Mean difference of ChromVAR-scores for TFs enriched in tumor-associated H3K4me3 signal versus H3K4me1 (left) and H3K27ac (right). o, scRNA-seq per-cell gene expression heatmap scaled across indicated myeloid subclusters in peripheral blood of human patients with NSCLC. Pooled from n = 4 patients. p, GREAT pathway terms enriched in indicated differentially accessible cisTopic region #5 of CD14+ monocytes from blood of patients with NSCLC (Fig. 1j). q, ChIP-X Enrichment Analysis (ChEA) calculated TF regulators for differentially expressed genes in CD14+ monocytes from blood of patients with NSCLC (n = 3) compared to healthy donors (n = 2). Dot color indicate major known biological pathways. Statistics computed by two-tailed Welch’s t-test (b), unpaired t-test with Holm-Sidak multiple comparison (c), unpaired two-tailed Student’s t-test (e), hypergeometric test with multiple test correction (g,h,k,j,p,q). error bars represent mean +/– SEM (c), colorscale indicates significance of motif enrichment based on hypergeometric test (j).
