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Authors
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Nadernezhad, A.; Kast, V. J.; Pette, D.; Baenke, F.; Stange, D. E.; Werner, C.; Lössner, D.
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Title
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Bottom-up programming of cell states in cancer organoids with defined synthetic adhesion cues
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Date
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14.04.2026
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Number
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0
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Abstract
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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.
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Publisher
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Wiley
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Wikidata
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Citation
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Advanced Materials 38 (2026) e17390
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DOI
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https://doi.org/10.1002/adma.202517390
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Tags
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