Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
12 05 2023
12 05 2023
Historique:
medline:
15
5
2023
pubmed:
11
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37167403
doi: 10.1126/science.add5327
pmc: PMC10316746
mid: NIHMS1900743
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadd5327Subventions
Organisme : NCI NIH HHS
ID : U54 CA274492
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA246901
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA233208
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NICHD NIH HHS
ID : DP1 HD084071
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209975
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
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