Sensing and guiding cell-state transitions by using genetically encoded endoribonuclease-mediated microRNA sensors.
Nat Biomed Eng
; 2024 Jul 09.
Article
en En
| MEDLINE
| ID: mdl-38982158
ABSTRACT
Precisely sensing and guiding cell-state transitions via the conditional genetic activation of appropriate differentiation factors is challenging. Here we show that desired cell-state transitions can be guided via genetically encoded sensors, whereby endogenous cell-state-specific miRNAs regulate the translation of a constitutively transcribed endoribonuclease, which, in turn, controls the translation of a gene of interest. We used this approach to monitor several cell-state transitions, to enrich specific cell types and to automatically guide the multistep differentiation of human induced pluripotent stem cells towards a haematopoietic lineage via endothelial cells as an intermediate state. Such conditional activation of gene expression is durable and resistant to epigenetic silencing and could facilitate the monitoring of cell-state transitions in physiological and pathological conditions and eventually the 'rewiring' of cell-state transitions for applications in organoid-based disease modelling, cellular therapies and regenerative medicine.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Nat Biomed Eng
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos