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LSD1 and CoREST2 Regulate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer[scMultiome-seq]

GSE268957 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 4 samples Submitted 2024/09/19 Platform GPL24676
Summary
Neuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EECs), the neuroendocrine cell of the normal colon epithelium, as compared to non-mucinous CRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. Here, single cell multi-omics was used to uncover epigenetic alterations that accompany EEC differentiation, identify STAT3 as a novel regulator of EEC specification, and discover a rare cancer-specific cell type with enteric neuron-like characteristics. Further experiments demonstrated that lysine-specific demethylase 1 (LSD1) and CoREST2 mediate STAT3 demethylation and regulate STAT3 chromatin binding. Knockdown of CoREST2 in an orthotopic xenograft mouse model resulted in decreased primary tumor growth and lung metastases. In culmination, these results provide rationale for new LSD1 inhibitors that target the interaction between LSD1 with STAT3 or CoREST2, which may improve clinical outcomes for patients with mCRC.
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Direct links to NCBI, no account and no request form: the whole study as GSE268957_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1119502 and SRA study SRP511457. Searching any of these in the dataset finder brings you back here.

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