Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.

ABSTRACT: During development, cell state transitions are coordinated through changes in the identity of molecular regulators in a cell type- and dose-specific manner. The ability to rationally engineer such transitions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein, we report the generation of synthetic gene circuits that can detect a desired cell state using AND-like logic integration of endogenous miRNAs (classifiers) and, upon detection, produce fine-tuned levels of output proteins using an miRNA-mediated output fine-tuning technology (miSFITs). Specifically, we created an "hPSC ON" circuit using a model-guided miRNA selection and circuit optimization approach. The circuit demonstrates robust PSC-specific detection and graded output prote

SUBMITTER: Prochazka L 

PROVIDER: S-EPMC9650275 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature