AI Article Synopsis
- - Trophoblast stem cells (TSCs) can be created from embryonic stem cells (ESCs) through chemical processes, but the mechanism linking the loss of stemness to TSC identity is not fully understood.
- - The study highlights the role of PRDM14, a key factor in maintaining pluripotency, which decreases during TSC formation due to activation of the Wnt/β-catenin signaling pathway.
- - This reduction of PRDM14 leads to changes in chromatin structure that trigger the expression of TSC transcription factors (like GATA3 and TFAP2C), suggesting that PRDM14 depletion is crucial for the transition from stemness to TSC formation.
Article Abstract
Trophoblast stem cells (TSCs) can be chemically converted from embryonic stem cells (ESCs) in vitro. Although several transcription factors (TFs) have been recognized as essential for TSC formation, it remains unclear how differentiation cues link elimination of stemness with the establishment of TSC identity. Here, we show that PRDM14, a critical pluripotent circuitry component, is reduced during the formation of TSCs. The reduction is further shown to be due to the activation of Wnt/β-catenin signaling. The extinction of PRDM14 results in the erasure of H3K27me3 marks and chromatin opening in the gene loci of TSC TFs, including GATA3 and TFAP2C, which enables their expression and thus the initiation of the TSC formation process. Accordingly, PRDM14 reduction is proposed here as a critical event that couples elimination of stemness with the initiation of TSC formation. The present study provides novel insights into how induction signals initiate TSC formation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074026 | PMC |
| http://dx.doi.org/10.1007/s00018-024-05237-9 | DOI Listing |
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