Engineering mouse cell fate controller by rational design.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39043686.
- Also identified by DOI 10.1038/s41467-024-50551-2 and PMC identifier 11266670.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller Nanog<sup>BiD</sup>, fusing BiD or BRG1 interacting domain of SS18 with Nanog. Nanog<sup>BiD</sup> promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.
Medical subject headings
- Transcription Factors
- Nanog Homeobox Protein