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

doi:10.1038/s41467-022-29857-6

	Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity
	Shi, Xiaohan 9; Li, Yunguang 7,8; Yuan, Qiuyue 5,6; Tang, Shijie 7,8; Guo, Shiwei 9; Zhang, Yehan 9; He, Juan 7,8; Zhang, Xiaoyu 7,8; Han, Ming 7,8; Liu, Zhuang 7,9
刊名	NATURE COMMUNICATIONS
	2022-04-21
卷号	13 期号:1 页码:16
DOI	10.1038/s41467-022-29857-6
英文摘要	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. The chromatin accessibility landscape and gene regulatory network of pancreatic cancer has not been fully characterised. Here, the authors perform multi-omics analysis of 84 pancreatic cancer organoid lines and reveal gene regulatory networks and distinct molecular subtypes.
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020905] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB38040400] ; National key research and development program of China[2017YFA0505500] ; National key research and development program of China[2020YFA0509000] ; National key research and development program of China[2020YFA0712402] ; Basic Frontier Science Research Program of Chinese Academy of Sciences[ZDBS-LY-SM015] ; National Natural Science Foundation of China[32125013] ; National Natural Science Foundation of China[81830054] ; National Natural Science Foundation of China[81772723] ; National Natural Science Foundation of China[31930022] ; National Natural Science Foundation of China[31771476] ; National Natural Science Foundation of China[12131020] ; National Natural Science Foundation of China[12026608] ; National Natural Science Foundation of China[82002559] ; National Natural Science Foundation of China[82172589] ; National Natural Science Foundation of China[81972913] ; National Natural Science Foundation of China[82172712] ; National Natural Science Foundation of China[12025107] ; National Natural Science Foundation of China[11871463] ; National Natural Science Foundation of China[61621003] ; Shanghai Science and Technology Committee[21XD1424200] ; Shanghai Science and Technology Committee[21ZR1470100] ; Shanghai Science and Technology Committee[20ZR1456500] ; Shanghai Science and Technology Committee[20511101200] ; JST Moonshot RD[JPMJMS2021] ; Shanghai ShenKang hospital development center[SHDC2020CR2001A]
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PORTFOLIO
WOS记录号	WOS:000785003900011
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/60378]
专题	中国科学院数学与系统科学研究院
通讯作者	Chen, Luonan; Wang, Yong; Jin, Gang; Gao, Dong
作者单位	1.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China 2.Guangdong Inst Intelligence Sci & Technol, Zhuhai 519031, Guangdong, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Key Lab Syst Biol, Hangzhou, Peoples R China 4.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 5.Univ Chinese Acad Sci, Sch Math Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Acad Math & Syst Sci, MDIS, HCMS,NCMIS,CEMS, Beijing 100080, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,Shanghai Key Lab Mol Andr, Shanghai 200031, Peoples R China 9.Naval Med Univ, Changhai Hosp, Dept Hepatobiliary Pancreat Surg, Mil Med Univ 2, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Shi, Xiaohan,Li, Yunguang,Yuan, Qiuyue,et al. Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity[J]. NATURE COMMUNICATIONS,2022,13(1):16.
APA	Shi, Xiaohan.,Li, Yunguang.,Yuan, Qiuyue.,Tang, Shijie.,Guo, Shiwei.,...&Gao, Dong.(2022).Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity.NATURE COMMUNICATIONS,13(1),16.
MLA	Shi, Xiaohan,et al."Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity".NATURE COMMUNICATIONS 13.1(2022):16.