caa a22 4500 528785184 20190713030951.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 10.3929/ethz-b-000115280 doi 10.1038/ncomms11247 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/115280 A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells [Elektronische Daten] [Pratik Saxena, Boon C. Heng, Peng Bai, Marc Folcher, Henryk Zulewski, Martin Fussenegger] Nat Commun Open access ethresearch Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets. Synthetic lineage-control networks may provide the missing link to genetically programme somatic cells into autologous cell phenotypes for regenerative medicine. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Saxena Pratik joint author Heng Boon C. joint author Bai Peng joint author Folcher Marc joint author Zulewski Henryk joint author Fussenegger Martin joint author Nature Communications London : Nature Publishing Group 7, p. 11247 2041-1723 http://hdl.handle.net/20.500.11850/115280 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/115280 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Saxena Pratik joint author ETHRESEARCH 700 1- Heng Boon C. joint author ETHRESEARCH 700 1- Bai Peng joint author ETHRESEARCH 700 1- Folcher Marc joint author ETHRESEARCH 700 1- Zulewski Henryk joint author ETHRESEARCH 700 1- Fussenegger Martin joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 7, p. 11247 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access