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

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

Authors:	Burdziak, C.; Alonso-Curbelo, D.; Walle, T.; Reyes, J.; Barriga, F. M.; Haviv, D.; Xie, Y.; Zhao, Z.; Zhao, C. J.; Chen, H. A.; Chaudhary, O.; Masilionis, I.; Choo, Z. N.; Gao, V.; Luan, W.; Wuest, A.; Ho, Y. J.; Wei, Y.; Quail, D. F.; Koche, R.; Mazutis, L.; Chaligné, R.; Nawy, T.; Lowe, S. W.; Pe'er, D.
Article Title:	Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis
Abstract:	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.
Keywords:	genetics; pancreatic neoplasms; pancreas; mouse; animal; animals; mice; carcinoma, pancreatic ductal; pathology; carcinogenesis; cell transformation, neoplastic; pancreas carcinoma; epigenesis, genetic; pancreas tumor; cell communication; genetic epigenesis; pancreatic ductal carcinoma; pancreatic carcinoma; neoplastic cell transformation
Journal Title:	Science
Volume:	380
Issue:	6645
ISSN:	0036-8075
Publisher:	American Association for the Advancement of Science
Date Published:	2023-05-12
Start Page:	eadd5327
Language:	English
DOI:	10.1126/science.add5327
PUBMED:	37167403
PROVIDER:	scopus
PMCID:	PMC10316746
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159739506&doi=10.1126%2fscience.add5327&partnerID=40&md5=2fbd90c9d5396ace501fee850d84d98e
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding author is MSK author Dana Pe'er -- Source: Scopus