Modulating myoblast differentiation with RNA-based controllers.
Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devic...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0275298 |
| _version_ | 1811194732678742016 |
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| author | Peter B Dykstra Thomas A Rando Christina D Smolke |
| author_facet | Peter B Dykstra Thomas A Rando Christina D Smolke |
| author_sort | Peter B Dykstra |
| collection | DOAJ |
| description | Tunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devices have been demonstrated in a number of systems showing proof-of-concept of applying ligand-responsive control over therapeutic activities, including regulation of cell fate decisions such as T cell proliferation and apoptosis. Here, we describe the application of a theophylline-responsive RNA device in a muscle progenitor cell system to control myogenic differentiation. Ribozyme-based RNA switches responsive to theophylline control fluorescent reporter expression in C2C12 myoblasts in a ligand dependent manner. HRAS and JAK1, both anti-differentiation proteins, were incorporated into RNA devices. Finally, we demonstrate that the regulation of HRAS expression via theophylline-responsive RNA devices results in the modulation of myoblast differentiation in a theophylline-dependent manner. Our work highlights the potential for RNA devices to exert drug-responsive, tunable control over cell fate decisions with applications in stem cell therapy and basic stem cell biology research. |
| first_indexed | 2024-04-12T00:31:31Z |
| format | Article |
| id | doaj.art-f42b87f3f06748c9a2cbd28d3b411a18 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T00:31:31Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f42b87f3f06748c9a2cbd28d3b411a182022-12-22T03:55:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179e027529810.1371/journal.pone.0275298Modulating myoblast differentiation with RNA-based controllers.Peter B DykstraThomas A RandoChristina D SmolkeTunable genetic controllers play a critical role in the engineering of biological systems that respond to environmental and cellular signals. RNA devices, a class of engineered RNA-based controllers, enable tunable gene expression control of target genes in response to molecular effectors. RNA devices have been demonstrated in a number of systems showing proof-of-concept of applying ligand-responsive control over therapeutic activities, including regulation of cell fate decisions such as T cell proliferation and apoptosis. Here, we describe the application of a theophylline-responsive RNA device in a muscle progenitor cell system to control myogenic differentiation. Ribozyme-based RNA switches responsive to theophylline control fluorescent reporter expression in C2C12 myoblasts in a ligand dependent manner. HRAS and JAK1, both anti-differentiation proteins, were incorporated into RNA devices. Finally, we demonstrate that the regulation of HRAS expression via theophylline-responsive RNA devices results in the modulation of myoblast differentiation in a theophylline-dependent manner. Our work highlights the potential for RNA devices to exert drug-responsive, tunable control over cell fate decisions with applications in stem cell therapy and basic stem cell biology research.https://doi.org/10.1371/journal.pone.0275298 |
| spellingShingle | Peter B Dykstra Thomas A Rando Christina D Smolke Modulating myoblast differentiation with RNA-based controllers. PLoS ONE |
| title | Modulating myoblast differentiation with RNA-based controllers. |
| title_full | Modulating myoblast differentiation with RNA-based controllers. |
| title_fullStr | Modulating myoblast differentiation with RNA-based controllers. |
| title_full_unstemmed | Modulating myoblast differentiation with RNA-based controllers. |
| title_short | Modulating myoblast differentiation with RNA-based controllers. |
| title_sort | modulating myoblast differentiation with rna based controllers |
| url | https://doi.org/10.1371/journal.pone.0275298 |
| work_keys_str_mv | AT peterbdykstra modulatingmyoblastdifferentiationwithrnabasedcontrollers AT thomasarando modulatingmyoblastdifferentiationwithrnabasedcontrollers AT christinadsmolke modulatingmyoblastdifferentiationwithrnabasedcontrollers |