Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis

被引：93

作者：

Burdziak, Cassandra ^{[1
,2
]}

Alonso-Curbelo, Direna ^{[3
,4
]}

Walle, Thomas ^{[1
,5
,6
,7
]}

Reyes, Jose ^{[1
,3
]}

Barriga, FranciscoM. ^{[3
]}

Haviv, Doron ^{[1
,2
]}

Xie, Yubin ^{[1
,2
]}

Zhao, Zhen ^{[3
,8
]}

Zhao, Chujun Julia ^{[1
,9
]}

Chen, Hsuan-An ^{[3
]}

Chaudhary, Ojasvi ^{[1
,10
]}

Masilionis, Ignas ^{[1
,10
]}

Choo, Zi-Ning ^{[1
]}

Gao, Vianne ^{[1
,2
]}

Luan, Wei ^{[3
]}

Wuest, Alexandra ^{[3
]}

Ho, Yu-Jui ^{[3
]}

Wei, Yuhong ^{[11
]}

Quail, Daniela F. ^{[11
]}

Koche, Richard ^{[12
]}

Mazutis, Linas ^{[1
,9
,13
]}

Chaligne, Ronan ^{[1
,10
]}

Nawy, Tal ^{[1
]}

Lowe, Scott W. ^{[3
,14
]}

Pe'er, Dana ^{[1
,14
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Computat & Syst Biol Program, New York, NY 10065 USA

[2] Weill Cornell Med, Tri Inst Training Program Computat Biol & Med, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10065 USA

[4] Inst Res Biomedicine IRB Barcelona, Barcelona Inst Sci & Technol, Barcelona 08028, Spain

[5] German Canc Res Ctr, Clin Cooperat Unit Virotherapy, D-69120 Heidelberg, Germany

[6] Univ Heidelberg Hosp, Dept Med Oncol, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany

[7] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[8] Icahn Sch Med Mt Sinai, Dept Pathol Mol & Cell Based Med, New York, NY 10029 USA

[9] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA

[10] Mem Sloan Kettering Canc Ctr, Alan & Sandra Gerry Metastasis & Tumor Ecosyst, New York, NY 10065 USA

[11] McGill Univ, Rosalind & Morris Goodman Canc Inst, Montreal, PQ H3A IA3, Canada

[12] Mem Sloan Kettering Canc Ctr, Ctr Epigenet Res, New York, NY 10065 USA

[13] Vilnius Univ, Life Sci Ctr, Inst Biotechnol, LT-02158 Vilnius, Lithuania

[14] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

SCIENCE | 2023年 / 380卷 / 6645期

基金：

美国国家卫生研究院;

关键词：

SOMATIC MUTATIONS; ONCOGENIC KRAS; CANCER; TUMOR; PROMOTES; INFLAMMATION; PROGRESSION; ROLES; STATE;

D O I：

10.1126/science.add5327

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed for diverse, late-emerging neoplastic fates and linked these to chromatin remodeling at cell-cell communication loci. Using an inference approach, we revealed signaling gene modules and tissue-level cross-talk, including a neoplasia-driving feedback loop between discrete epithelial and immune cell populations that was functionally validated in mice. Our results uncover a neoplasia-specific tissue-remodeling program that may be exploited for pancreatic cancer interception. Copyright © 2023 the authors, some rights reserved.

引用

页码：597 / +

页数：15

共 69 条

[1] Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer [J].

Alam, Aftab ;

Levanduski, Eric ;

Denz, Parker ;

Villavicencio, Helena Solleiro ;

Bhatta, Maulasri ;

Alhorebi, Lamees ;

Zhang, Yali ;

Gomez, Eduardo Cortes ;

Morreale, Brian ;

Senchanthisai, Sharon ;

Li, Jun ;

Turowski, Steven G. ;

Sexton, Sandra ;

Sait, Sheila Jani ;

Singh, Prashant K. ;

Wang, Jianmin ;

Maitra, Anirban ;

Kalinski, Pawel ;

DePinho, Ronald A. ;

Wang, Huamin ;

Liao, Wenting ;

Abrams, Scott I. ;

Segal, Brahm H. ;

Dey, Prasenjit .

CANCER CELL, 2022, 40 (02) :153-+

[2] Network motifs: theory and experimental approaches [J].

Alon, Uri .

NATURE REVIEWS GENETICS, 2007, 8 (06) :450-461

[3] A gene-environment-induced epigenetic program initiates tumorigenesis [J].

Alonso-Curbelo, Direna ;

Ho, Yu-Jui ;

Burdziak, Cassandra ;

Maag, Jesper L. V. ;

Morris, John P. ;

Chandwani, Rohit ;

Chen, Hsuan-An ;

Tsanov, Kaloyan M. ;

Barriga, Francisco M. ;

Luan, Wei ;

Tasdemir, Nilgun ;

Livshits, Geulah ;

Azizi, Elham ;

Chun, Jaeyoung ;

Wilkinson, John E. ;

Mazutis, Linas ;

Leach, Steven D. ;

Koche, Richard ;

Pe'er, Dana ;

Lowe, Scott W. .

NATURE, 2021, 590 (7847) :642-648

[4] Molecular mechanisms of IL-33-mediated stromal interactions in cancer metastasis [J].

Andersson, Patrik ;

Yang, Yunlong ;

Hosaka, Kayoko ;

Zhang, Yin ;

Fischer, Carina ;

Braun, Harald ;

Liu, Shuzhen ;

Yu, Guohua ;

Liu, Shihai ;

Beyaert, Rudi ;

Chang, Mayland ;

Li, Qi ;

Cao, Yihai .

JCI INSIGHT, 2018, 3 (20)

[5] Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment [J].

Azizi, Elham ;

Carr, Ambrose J. ;

Plitas, George ;

Cornish, Andrew E. ;

Konopacki, Catherine ;

Prabhakaran, Sandhya ;

Nainys, Juozas ;

Wu, Kenmin ;

Kiseliovas, Vaidotas ;

Setty, Manu ;

Choi, Kristy ;

Fromme, Rachel M. ;

Phuong Dao ;

McKenney, Peter T. ;

Wasti, Ruby C. ;

Kadaveru, Krishna ;

Mazutis, Linas ;

Rudensky, Alexander Y. ;

Pe'er, Dana .

CELL, 2018, 174 (05) :1293-+

[6] p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells [J].

Bailey, J. M. ;

Hendley, A. M. ;

Lafaro, K. J. ;

Pruski, M. A. ;

Jones, N. C. ;

Alsina, J. ;

Younes, M. ;

Maitra, A. ;

McAllister, F. ;

Iacobuzio-Donahue, C. A. ;

Leach, S. D. .

ONCOGENE, 2016, 35 (32) :4282-4288

[7] MetaCell: analysis of single-cell RNA-seq data using K-nn graph partitions [J].

Baran, Yael ;

Bercovich, Akhiad ;

Sebe-Pedros, Arnau ;

Lubling, Yaniv ;

Giladi, Amir ;

Chomsky, Elad ;

Meir, Zohar ;

Hoichman, Michael ;

Lifshitz, Aviezer ;

Tanay, Amos .

GENOME BIOLOGY, 2019, 20 (01)

[8] Generalizing RNA velocity to transient cell states through dynamical modeling [J].

Bergen, Volker ;

Lange, Marius ;

Peidli, Stefan ;

Wolf, F. Alexander ;

Theis, Fabian J. .

NATURE BIOTECHNOLOGY, 2020, 38 (12) :1408-1414

[9]

Burdziak, 2023, ZENODO, DOI [10.5281/zenodo.7874129, DOI 10.5281/ZENODO.7874129]

[10] The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia [J].

Carriere, Catherine ;

Seeley, Elliott S. ;

Goetze, Tobias ;

Longnecker, Daniel S. ;

Korc, Murray .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (11) :4437-4442

← 1 2 3 4 5 6 7 →