Chemogenetic tuning reveals optimal MAPK signaling for cell-fate programming.

ABSTRACT: Cell states evolve through the combined activity of signaling pathways and gene networks. While transcription factors can direct cell fate, these factors rely on a receptive cell state. How signaling levels contribute to the emergence of receptive cell states remains poorly defined. Using a well-defined model of direct conversion, we examined how levels of the mitogen-activated protein kinase (MAPK)-activating oncogene HRAS^G12V influence direct conversion of primary fibroblasts to induced motor neurons. The rates of direct conversion respond biphasically to increasing HRAS^G12V levels. An optimal "Goldilocks" level of MAPK signaling efficiently drives cell-fate programming, whereas high levels of HRAS^G12V induce senescence. Through chemogenetic tuning, we se

SUBMITTER: Lende-Dorn BA 

PROVIDER: S-EPMC12571515 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature