PATCH treatment in vivo
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1301124 | ENA |
REPOSITORIES: ENA
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Project description:We employed MNase-seq and ChIP-seq to determine irregularities in chromatin architecture in mutants of the nucleosome acidic patch. Indeed, the acidic patch mutant showed defects in nucleosome positioning and occupancy at genes with high expression and H2B K123ub levels, linking the acidic patch to transcription-dependent chromatin changes. Our results emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.
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Project description:The H2A variant H2AZ is essential for embryonic development and for proper execution of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions in H2AZ are likely key for its functional specialization, but we know little about how these differences contribute to chromatin regulation. Here, we show that the extended acidic patch, specifically the three divergent residues in the C-terminal docking domain, is necessary for lineage commitment during ESC differentiation and proper execution of gene expression programs during ESC differentiation. Surprisingly, disruption of the acidic patch domain has a distinct consequence on cellular specification compared to H2AZ depletion. This is consistent with differences in gene expression profiles of H2AZ M-bM-^@M-^Sdepleted and acidic patch (AP) mutant ESCs during early lineage commitment. Interestingly, the distinct consequence of AP mutant expression on gene regulation is coincidence with an altered destabilized chromatin state and high chromatin mobility dependent on active transcription. Collectively, our data shows that the divergent residues within the acidic patch domain are key structural determinants of H2AZ function and links chromatin structure and dynamics with gene regulation and cell fate specification. H2AZ extended acidic patch was mutated, or H2AZ was KD in mouse embryonic stem cells and RNA-Seq analysis was performed on the resulting cultures. Characterization of H2AZ-WT and -AP3-mutant binding specificities were performed by ChIP-Seq.
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Project description:Microneedle patches are widely employed in pain-free drug delivery, biosensing, and cosmetic applications. However, weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Here, mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In the challenging working condition of animal hearts beat with large cyclic strains, the barbs provided 0.4 N interlocking force, which resulted in firm fixation of the bioinspired microneedle patch. In addition, the minimal bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate between microneedles to the epicardium via coagulation. In the demonstrative application of myocardial infarction treatment, the microneedle patches significantly reduced cardiac wall stress and strain in the infarct and border zone, maintaining left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart free of sutures and adhesives, and the fixation step only took 2 minutes. Therefore, the honeybee stinger inspired microneedles could provide an adaptive and convenient means to adhere patches for various medical applications.
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