ArticleStem cell reports2026
Integration of the naive pluripotency gene network with the response to GSK3 inhibition by Tcf7l1-driven enhancer decommissioning.
Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
The transition out of naive pluripotency requires the simultaneous dissolution of the naive gene regulatory network as well as a redirection of transcriptional response to WNT/β-CATENIN signaling. Here, we show that Tcf7l1 functions as a linchpin factor that connects the two outcomes via effects at TCF7L1-bound cis-regulatory elements in mouse pluripotent stem cells. A combination of gene knockout and inducible expression lines of ESCs was generated to experimentally isolate effects of Tcf/Lef factors on pluripotency. Naive cis-regulatory elements were specifically bound by and rapidly decommissioned by TCF7L1 upon releasing cells from GSK3 inhibition. These findings suggest that Tcf7l1-mediated enhancer decommissioning serves as a critical mechanism by which pluripotent cells rapidly alter the response to signaling pathways in preparation for gastrulation, and it may be a mechanism used in diverse cell types for modulating the effects of WNT/β-CATENIN signaling pathway in a cell-specific manner to stimulate a variety of cell fate decisions.
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