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Wiedenmann, S. ; Breunig, M.* ; Merkle, J.* ; von Toerne, C. ; Georgiev, T. ; Moussus, M. ; Schulte, L.N.* ; Seufferlein, T.* ; Sterr, M. ; Lickert, H. ; Weissinger, S.E.* ; Möller, P.* ; Hauck, S.M. ; Hohwieler, M.* ; Kleger, A.* ; Meier, M.

Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip.

Nat. Bio. Eng., DOI: 10.1038/s41551-021-00757-2 (2021)
Creating in vitro models of diseases of the pancreatic ductal compartment requires a comprehensive understanding of the developmental trajectories of pancreas-specific cell types. Here we report the single-cell characterization of the differentiation of pancreatic duct-like organoids (PDLOs) from human induced pluripotent stem cells (hiPSCs) on a microwell chip that facilitates the uniform aggregation and chemical induction of hiPSC-derived pancreatic progenitors. Using time-resolved single-cell transcriptional profiling and immunofluorescence imaging of the forming PDLOs, we identified differentiation routes from pancreatic progenitors through ductal intermediates to two types of mature duct-like cells and a few non-ductal cell types. PDLO subpopulations expressed either mucins or the cystic fibrosis transmembrane conductance regulator, and resembled human adult duct cells. We also used the chip to uncover ductal markers relevant to pancreatic carcinogenesis, and to establish PDLO co-cultures with stellate cells, which allowed for the study of epithelial-mesenchymal signalling. The PDLO microsystem could be used to establish patient-specific pancreatic duct models.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gene Copy Number; Enrichment Analysis; Protein Expression; Web Server; Mouse; Progenitors; Model; Generation; Biomarkers; Laminin-1
ISSN (print) / ISBN 2157-846X
e-ISSN 2157-846X
Verlag Nature Publishing Group
Verlagsort London ; New York NY ; Tokyo
Begutachtungsstatus Peer reviewed
Förderungen Baden-Württemberg Stiftung (Baden-Württemberg Foundation)
Deutsche Forschungsgemeinschaft (German Research Foundation)