Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity.

Abstract

Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

• Authors: Xiaohan Shi, Yunguang Li, Qiuyue Yuan, Shijie Tang, Shiwei Guo, Yehan Zhang, Juan He, Xiaoyu Zhang, Ming Han, Zhuang Liu, Yiqin Zhu, Suizhi Gao, Huan Wang, Xiongfei Xu, Kailian Zheng, Wei Jing, Luonan Chen, Yong Wang, Gang Jin, Dong Gao
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 2169 (04 21 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35449156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Chromatin

Topics

• Chromatin (genetics)
• Gene Regulatory Networks
• Humans
• Organoids
• Pancreatic Neoplasms (drug therapy, genetics)
• Transcriptome
• Pancreatic Neoplasms