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Engineering mouse cell fate controller by rational design
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DOI：10.1038/s41467-024-50551-2.png)
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摘要
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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 NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD 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. Cell fate is principally regulated by a common machine or cell-intrinsic machine. Here the authors report the design and testing of an engineered chromatin controller to drive such machine for mouse cell fate transition in precision.
Keyword:
CHROMATIN ACCESSIBILITY DYNAMICS
PLURIPOTENT STEM-CELLS
SOMATIC-CELLS
NANOG
FIBROBLASTS
INDUCTION
BINDING
HISAT
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IF:
15.7
论文数:
9.4W
被引数:
91.2W
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