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| Home > Publications database > Bottom-Up Programming of Cell States in Cancer Organoids with Defined Synthetic Adhesion Cues. |
| Journal Article | DKFZ-2026-00867 |
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2026
Wiley-VCH
Weinheim
Abstract: Despite advances in defined culture systems, current organoid models lack programmable control of transcriptomic states beyond fixed genetic constraints or broadly specific microenvironmental conditions. Here, a bottom-up biomaterial-based platform is introduced to program cell state changes in pancreatic cancer organoids by tuning minimal adhesion cues within a synthetic matrix. A Design of Experiments framework is used to systematically model the patient-specific transcriptome-wide impact of matrix-presented adhesion cues. Focusing on epithelial-mesenchymal transition (EMT) as a proof-of-concept cellular program, a multiobjective optimization approach is applied to identify patient-specific matrix compositions that enrich EMT-associated transcriptional programs. Organoids cultured in these optimized matrices exhibit transcriptomic signatures consistent with EMT enrichment and coordinated shift in EMT-associated regulatory signatures. Secretome profiling further reveals changes in cytokines previously linked to EMT-associated inflammatory, hypoxia, and TGF-β signaling. Together, these findings demonstrate that quantitative and targeted modulation of defined adhesion cues enables programmable control of transcriptomic states in pancreatic cancer organoids.
Keyword(s): computational biomaterials design ; organoid microenvironment engineering ; patient‐derived cancer organoids ; synthetic extracellular matrix ; transcriptomic state programming
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