AI Article Synopsis
- Klf5 is crucial for maintaining the proliferation and pluripotency of trophoblast stem cells (TSCs), which are essential for proper placental development and fetal growth.
- Klf5 knockdown leads to a decrease in TSC-specific gene expression, resulting in rapid differentiation and inability to establish TSCs in vitro.
- The mechanism involves Klf5 promoting an open chromatin state and maintaining histone modifications that enhance transcription of pluripotency genes, suggesting its importance in regulating TSC self-renewal and placental health.
Article Abstract
The effective proliferation and differentiation of trophoblast stem cells (TSCs) is indispensable for the development of the placenta, which is the key to maintaining normal fetal growth during pregnancy. Kruppel-like factor 5 (Klf5) is implicated in the activation of pluripotency gene expression in embryonic stem cells (ESCs), yet its function in TSCs is poorly understood. Here, we showed that Klf5 knockdown resulted in the downregulation of core TSC-specific genes, consequently causing rapid differentiation of TSCs. Consistently, Klf5-depleted embryos lost the ability to establish TSCs in vitro. At the molecular level, Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes. Deprivation of Klf5 impaired the enrichment of p300, a major histone acetyl transferase of H3 lysine 27 acetylation (H3K27ac), and further reduced the occupancy of H3K27ac at promoter regions, leading to decreased transcriptional activity of TSC pluripotency genes. Thus, our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs and provide a reference for understanding placental development and improving pregnancy rates.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768793 | PMC |
| http://dx.doi.org/10.1093/jmcb/mjad045 | DOI Listing |
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