scPRIME-seq uncovers synchronized multimodal molecular collapse facilitated by pre-neoplastic epigenetic burden in prostate cancer
- 1Shanghai Institute of Biochemistry and Cell Biology, CAS
Abstract
Tumorigenesis involves alterations across the genome, epigenome and transcriptome, yet how these layers interact to drive malignant transformation remains unclear, largely due to the lack of scalable multimodal single-cell approaches. Here, we developed scPRIME-seq, a high-throughput platform for simultaneous single-cell profiling of transcriptome, genome and DNA methylome, and applied it to 436,908 cells from 29 prostate cancers and 15 benign tissues. This multimodal atlas resolved dynamic changes across 30 cell types and a unified tumorigenic trajectory. Integrated analysis revealed a cell-state transition tipping point, where the onset of aneuploidy is temporally coupled with global methylomic alterations and transcriptomic rewiring. Early focal epigenetic alterations, including TMEM106A promoter hypermethylation and the emergence of hypomethylated domains, were present in founder aneuploid clones and benign tissues, indicating a pre-neoplastic origin of epigenetic burden. These pre-neoplastic alterations coincide with transcriptomic changes that affect epithelial interactions with stromal and immune compartments, promoting a putative tumor-permissive microenvironment. scPRIME-seq provides a high-throughput multimodal framework for identifying conserved, cell-intrinsic molecular programs underlying tumorigenesis.
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BibTeX
@misc{li2026scprimeseq,
title = {{scPRIME-seq uncovers synchronized multimodal molecular collapse facilitated by pre-neoplastic epigenetic burden in prostate cancer}},
author = {S. Li and Z. Liu and Y. Xie and X. Ma and M. Tan and X. Wang and H. Ye and D. Wu and S. Huang and Z. Li},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757464},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757464v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - scPRIME-seq uncovers synchronized multimodal molecular collapse facilitated by pre-neoplastic epigenetic burden in prostate cancer
AU - S. Li
AU - Z. Liu
AU - Y. Xie
AU - X. Ma
AU - M. Tan
AU - X. Wang
AU - H. Ye
AU - D. Wu
AU - S. Huang
AU - Z. Li
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757464
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757464v1
AB - Tumorigenesis involves alterations across the genome, epigenome and transcriptome, yet how these layers interact to drive malignant transformation remains unclear, largely due to the lack of scalable multimodal single-cell approaches. Here, we developed scPRIME-seq, a high-throughput platform for simultaneous single-cell profiling of transcriptome, genome and DNA methylome, and applied it to 436,908 cells from 29 prostate cancers and 15 benign tissues. This multimodal atlas resolved dynamic changes across 30 cell types and a unified tumorigenic trajectory. Integrated analysis revealed a cell-state transition tipping point, where the onset of aneuploidy is temporally coupled with global methylomic alterations and transcriptomic rewiring. Early focal epigenetic alterations, including TMEM106A promoter hypermethylation and the emergence of hypomethylated domains, were present in founder aneuploid clones and benign tissues, indicating a pre-neoplastic origin of epigenetic burden. These pre-neoplastic alterations coincide with transcriptomic changes that affect epithelial interactions with stromal and immune compartments, promoting a putative tumor-permissive microenvironment. scPRIME-seq provides a high-throughput multimodal framework for identifying conserved, cell-intrinsic molecular programs underlying tumorigenesis.
ER -