Fig. 5
EMP transcriptional memory is enriched in metastatic castrate-resistant prostate cancer. a Principal component analysis as cells undergo transition from an epithelial (No Dox; D0) to a mesenchymal (EMT5; E5) and back to an epithelial (MErT; M3–20) state. b Heatmap showing differential transcript expression between MErT20 (M20) and No Dox (D0) (1564 gene identities can be found in the supplementary dataset 1). Heatmap color refers to normalised z-score. c Activation scores of upstream regulators in transcripts differential in EMT5 (E5) vs No Dox (D0) and MErT20 (M20) vs No Dox (D0). d Transcriptional clusters representing persistent transcript alterations. Cluster VII shows transcripts that remained upregulated and Cluster VIII shows transcripts that remained downregulated during the 20 day MErT. Cluster IX shows transcripts that were unaltered during EMT (E5) and then became newly activated by 3 days of MErT (M3) and remained for 5 and 20 days (M3,5–20). Cluster X shows transcripts that were unaltered during EMT (E5) and then became newly repressed by 3 days of MErT (M3) and remained for 5 and 20 days (M5–20). Cluster avg is the average transcriptional pattern of the transcript cluster. Heatmaps represent gene expression within Clusters VII and VIII, and within clusters IX and X. Heatmap color refers to normalised z-score. e Enrichment score of the (ei) EMT persistent (Clusters VII/VIII combined) and (eii) MErT unique (Clusters IX/X combined) signatures in samples of localised PCa and mCRPC from the Grasso dataset [23]. f Correlation plot of the EMT persistent and MErT unique signature scores in (fi) localised PCa and mCRPC samples (fii), and benign prostate tissue from the Grasso dataset. Error bars indicate SEM. **** p < 0.0001; unpaired t-test. g Immunohistochemical staining of POU4F1 and TUBB3 in samples from treatment naïve patients, and during neoadjuvant hormone therapy (NHT). Breakdown of patient numbers can be found in Table S3. Scale bars are 100 µm
