TY  - JOUR
AU  - Burdziak, Cassandra
AU  - Alonso-Curbelo, Direna
AU  - Walle, Thomas
AU  - Reyes, José
AU  - Barriga, Francisco M
AU  - Haviv, Doron
AU  - Xie, Yubin
AU  - Zhao, Zhen
AU  - Zhao, Chujun Julia
AU  - Chen, Hsuan-An
AU  - Chaudhary, Ojasvi
AU  - Masilionis, Ignas
AU  - Choo, Zi-Ning
AU  - Gao, Vianne
AU  - Luan, Wei
AU  - Wuest, Alexandra
AU  - Ho, Yu-Jui
AU  - Wei, Yuhong
AU  - Quail, Daniela F
AU  - Koche, Richard
AU  - Mazutis, Linas
AU  - Chaligné, Ronan
AU  - Nawy, Tal
AU  - Lowe, Scott W
AU  - Pe'er, Dana
TI  - Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis.
JO  - Science
VL  - 380
IS  - 6645
SN  - 0036-8075
CY  - Cambridge, Mass.
PB  - Moses King
M1  - DKFZ-2023-00960
SP  - eadd5327
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37167403
DO  - DOI:10.1126/science.add5327
UR  - https://inrepo02.dkfz.de/record/275980
ER  -