Genetic control couples TGFβ-independent pluripotent stem cell renewal to deterministic forward programming across germ layers

GERALT couples TGFβ-independent, NANOG-supported hiPSC renewal to doxycycline-inducible lineage programming, maintaining pluripotency during extended TGFβ withdrawal while enabling myogenic, neuronal, and hepatic differentiation.

• Why it matters: Expansion of hiPSCs still depends on extracellular growth factors, limiting reproducibility and scalability; genetic control of renewal could reduce process complexity and operator dependence.
• What they did: The GERALT push-pull genetic circuit was assembled via targeted safe-harbour integration, using NANOG-supported renewal with simultaneous NANOG silencing and doxycycline-inducible lineage programming across adherent and suspension culture.
• The result: GERALT maintained pluripotency during extended TGFβ withdrawal and, versus OPTi-OX in myogenesis, enabled differentiation in simplified medium while canalising and accelerating commitment, including suspension myogenic programming and hydrogel in-tissue programming for electrically responsive engineered muscle tissues.