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Investigate FOXA2-driven lineage plasticity in prostate cancer cells by Single-cell nanopore RNA sequencing (scNanoRNA-seq)

GSE289790 Homo sapiens (human) Single-cell RNA-seq 2 samples Submitted 2025/06/06 Platform GPL26167
At a glance

Single-cell RNA-seq · human · 2 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Homo sapiens (human)
Samples
2 samples
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
NKX2-1 drives neuroendocrine transdifferentiation of prostate cancer via epigenetic and 3D chromatin remodelingNature genetics · 2025
Summary (written by the submitters)
Emerging evidence suggests that the epigenetic state, including the DNA methylation, chromatin accessibility and histone modification, is substantially remodeled, leading to transcriptional reprogramming during the transformation of castration resistant adenocarcinoma (CRPC-Adeno) to neuroendocrine (CRPC-NE) lineage and LUAD to LUAD-SCLC lineage .
Read the full summary ↓
However, the underlying mechanism is largely unknown. Here, we found FOXA2 transdifferentiates prostate adenocarcinoma away from an AR+/AR gene signature positive (AR+/ARS+) luminal cell lineage to an embryonic and neuroendocrine-lineage by inducing a population of AR+/ARS- transient cells through NKX2-1. Mechanistically, as a pioneer factor, FOXA2 primes NE lineage enhancers by inducing regional chromatin accessibility and DNA demethylation at early stage of transformation. Whereas, once the expression of NKX2-1 is induced by FOXA2, FOXA2 interacts with NKX2-1, mediates gene promoter and enhancer looping and cooperatively recruits P300/CBP complex to NE lineage enhancers, thereby activates NE lineage gene transcription. Interestingly, similar mechanism is also observed in SCLC cancer, suggesting FOXA2 and NKX2-1 are general regulators orchestrating the epigenetic landscape of NE lineage cancer. Finally, therapeutic targeting P300/CBP with CCS1477 which is in clinical trial for lethal PCa significantly impairs NEPC tumor growth.
Published in
NKX2-1 drives neuroendocrine transdifferentiation of prostate cancer via epigenetic and 3D chromatin remodeling
Lu X, Keo V, Cheng I et al. · Nature genetics 2025 · PMID 40691407 · doi:10.1038/s41588-025-02265-4
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE289790_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1224796 and SRA study SRP564391. Searching any of these in the dataset finder brings you back here.

Samples in this study

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