A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785184 | ||
| 005 | 20190713030951.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2016 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000115280 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms11247 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/115280 | ||
| 245 | 0 | 2 | |a A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells |h [Elektronische Daten] |c [Pratik Saxena, Boon C. Heng, Peng Bai, Marc Folcher, Henryk Zulewski, Martin Fussenegger] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Saxena |D Pratik |e joint author | |
| 700 | 1 | |a Heng |D Boon C. |e joint author | |
| 700 | 1 | |a Bai |D Peng |e joint author | |
| 700 | 1 | |a Folcher |D Marc |e joint author | |
| 700 | 1 | |a Zulewski |D Henryk |e joint author | |
| 700 | 1 | |a Fussenegger |D Martin |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 7, p. 11247 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/115280 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/115280 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Saxena |D Pratik |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Heng |D Boon C. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Bai |D Peng |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Folcher |D Marc |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Zulewski |D Henryk |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Fussenegger |D Martin |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 7, p. 11247 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||