Fig. 3: Absence of caspase 8 promotes epigenetic reprogramming towards a stem cell-like state and phenocopies transcriptional profiles of human metastatic and relapse SCLC. | Nature Communications

Fig. 3: Absence of caspase 8 promotes epigenetic reprogramming towards a stem cell-like state and phenocopies transcriptional profiles of human metastatic and relapse SCLC.

From: Lack of caspase 8 directs neuronal progenitor-like reprogramming and small cell lung cancer progression

Fig. 3: Absence of caspase 8 promotes epigenetic reprogramming towards a stem cell-like state and phenocopies transcriptional profiles of human metastatic and relapse SCLC.The alternative text for this image may have been generated using AI.

a Enriched pathways within the top 50 upregulated and b downregulated genes in RPC-derived cell lines. c RPC-derived cell lines (n = 4) as compared to RP-derived cell lines (n = 4) were subjected to MeDip-Seq. Differentially methylated regions (DMRs) within promotor regions between the 4 RP and 4 RPC cell lines are shown. Blue and red colors show increased hypomethylation and hypermethylation respectively, in RPC cell lines. d Venn diagrams of the overlap between significantly hypomethylated and significantly upregulated Gene Ontology terms in RPC cells (p = 2.68e–08) and e between significantly hypermethylated and significantly downregulated Gene Ontology terms in RPC cells (p = 2.54e–23). f RPC-derived cell lines (n = 4) as compared to RP-derived cell lines (n = 4) were subjected to spheroid assays for the indicated time. Data are means ± SEM of three replicates per cell line per time point of a representative experiment. Representative images of RP (upper) or RPC (lower) tumor spheroids at the last time point. Scale bars: images on the left: 1000 μm, images on the right: 100 μm. g RP (n = 4) and RPC (n = 4) cell lines were cultured for 3 weeks in osteocyte differentiation media and subsequently stained with Alizarin Red. Data are presented as mean values of positive cells per well ± SEM. h RP- (n = 3) and RPC-derived cell lines (n = 3) were treated with cisplatin [20 μM]/ etoposide [10 μM], DRAQ7 was added to each well [100 nM] and live cell imaging (IncuCyte) was used to quantify dead cells (DRAQ7+) normalized to confluency. Data are means ± SEM of 3 biological replicates in 3 different cell lines per genotype. i Human SCLC patient RNA-seq data20 (n = 52) were analyzed and clustered by transcriptional profiles up- and down-regulated in RPC versus RP mice from snRNA-seq pseudo-bulk. a, b Benjamini-Hochberg false discovery rate (FDR) correction was used to adjust for multiple testing. d, e Fisher´s exact test f–h two-tailed unpaired t tests. Source Data are provided as a Source Data file.

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