EDC4 C-terminal domain scaffolds P-body assembly and links P-body dynamics to p53 mediated tumor suppression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1164755 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR30786051_1.fastq.gz | Fastqsanger.gz | |||
| SRR30786051_2.fastq.gz | Fastqsanger.gz | |||
| SRR30786052_1.fastq.gz | Fastqsanger.gz | |||
| SRR30786052_2.fastq.gz | Fastqsanger.gz |
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Project description:Processing bodies (P-bodies) are membrane-less organelles involved in mRNA metabolism, including decay, storage, and translational repression. Their formation is driven by liquid-liquid phase separation, primarily mediated by the scaffold protein EDC4. This study identifies the C-terminal domain of EDC4 as essential for P-body assembly. Introducing the microprotein NBDY selectively disrupted P-body formation by inhibiting EDC4 self-interaction, without affecting mRNA decay. Disruption of P-bodies led to upregulation of genes in the p53 signaling pathway, highlighting a link between P-body dynamics and tumor suppression. Clinical data suggest a possible connection between P-body dysregulation and cancer progression.
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Project description:This study investigated early host reactions to implanted materials to predict successful tissue regeneration with implant. Three kinds of scaffold, i.e., non-coat, collagen-coated, and PMB-coated porous polystylene scaffolds were implanted subcutaneously in mice dorsal area. Those scaffolds were used as bio-incomopatible materials, appropriate materials for tissue regeneration (bio active), and inappropriate to regenration (bio-inert) scaffolds. Seven days after implantation, scaffolds were explanted and total RNA was isolated from infiltrated host cells into scaffold by laser microdissection. Gene expressions of cells in collagen- and PMB-coated scaffold were normalized using results of non coat scaffold. Genes with more than 2-fold difference between collagen and PMB were picked up and narrowed to related keywords; inflammation, angiogenesis, wound healing, and mcrophage polarization. Among those genes, interluekin (IL)-1beta which promote both inflammation and wound healing was up-regulated in collagen-coated scaffold. On the other hand, IL-10 which suppress both inflammation and wound healing was up-regulated in PMB-coated scaffold. Angiogenesis-promoting genes were up-regulated and angiogenesis suppressve genes were suppressed in collagen. Up-regulation of IL-1b and the angiogenesis-relating genes inside the porous scaffolds are the possibly important factors for controlling tissue regeneration. Three-condition experiment, host cells infiltrated in non coat (reference), collagen-coated, and PMB-coated scaffolds. Two-microarray condition experiments, collagen vs. non coat and PMB coat vs. non coat. Hybridization: 2 replicates. Scanning: 3 replicates. Biological experiments: once.
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Project description:Retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSCs), called iRPE, are being explored as a cell-based therapy for the treatment of retinal degenerative diseases, especially age-related macular degeneration (AMD). The success of RPE implantation is believed to be linked to the use of biomimetic scaffolds that simulate Bruch’s membrane and aid in its maturation and integration. Current practices widely utilize fibrous scaffolds from synthetic polymers, such as polycaprolactone (PCL), rather than from natural biomaterials. Here, we tested the hypothesis that naturally derived fibrous scaffolds, with their unique translational potential, can provide favorable conditions permissive for the maturation of iRPE in vitro. We show that the culture of iRPE on natural, soy protein-derived nanofibrous scaffolds match the results of similar cells cultured on synthetic PCL nanofibrous scaffolds. The mechanical properties of soy scaffolds better emulate the native Bruch’s membrane, which would likely limit the foreign body reaction triggered by mismatch of host and biomaterial strength. Additionally, soy scaffolds exhibit unique biochemistry that improves biocompatibility and have tunable crosslinking to control degradation rates. Comparative transcriptome analysis demonstrates that iRPE maturation on nanofibrous scaffolds, either natural or synthetic, yielded more consistent outcomes than on other non-fibrous substrates. Taken together, our studies suggest that the maturation of cultured RPE for subsequent clinical applications will benefit from the use of nanofibrous scaffolds derived from natural proteins.
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