PDGFRβ Activation Induced the Bovine Embryonic Genome Activation via Enhanced NFYA Nuclear Localization.
Chalani Dilshani PereraMuhammad IdreesAbdul Majid KhanZaheer HaiderSafeer UllahJi-Su KangSeo-Hyun LeeSeon-Min KangIl-Keun KongPublished in: International journal of molecular sciences (2023)
Embryonic genome activation (EGA) is a critical step during embryonic development. Several transcription factors have been identified that play major roles in initiating EGA; however, this gradual and complex mechanism still needs to be explored. In this study, we investigated the role of nuclear transcription factor Y subunit A (NFYA) in bovine EGA and bovine embryonic development and its relationship with the platelet-derived growth factor receptor-β (PDGFRβ) by using a potent selective activator (PDGF-BB) and inhibitor (CP-673451) of PDGF receptors. Activation and inhibition of PDGFRβ using PDGF-BB and CP-673451 revealed that NFYA expression is significantly ( p < 0.05) affected by the PDGFRβ. In addition, PDGFRβ mRNA expression was significantly increased ( p < 0.05) in the activator group and significantly decreased ( p < 0.05) in the inhibitor group when compared with PDGFRα. Downregulation of NFYA following PDGFRβ inhibition was associated with the expression of critical EGA-related genes, bovine embryo development rate, and implantation potential. Moreover, ROS and mitochondrial apoptosis levels and expression of pluripotency-related markers necessary for inner cell mass development were also significantly ( p < 0.05) affected by the downregulation of NFYA while interrupting trophoblast cell ( CDX2 ) differentiation. In conclusion, the PDGFRβ-NFYA axis is critical for bovine embryonic genome activation and embryonic development.
Keyphrases
- growth factor
- transcription factor
- poor prognosis
- single cell
- oxidative stress
- cell proliferation
- cell death
- smooth muscle
- genome wide
- signaling pathway
- binding protein
- stem cells
- cell therapy
- endoplasmic reticulum stress
- dna damage
- mesenchymal stem cells
- pregnant women
- risk assessment
- inflammatory response
- nuclear factor
- drug induced
- recombinant human
- pi k akt
- genome wide identification