Biology subjects

Sevinc, K.

Publications and source records attributed to Sevinc, K..

3 recordsLinked to original sources

bioRxiv2023

ACE2-Coated Virus-Like Particles Effectively Block SARS-CoV-2 Infection

A large body of research accumulated over the past three years dedicated to our understanding and fighting COVID-19. Blocking the interaction between SARS-CoV-2 Spike and ACE2 receptor has been considered an effective strategy as anti-SARS-CoV-2 therapeutics. In this study, we developed ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. These ACE2-VLPs exhibited high neutralization capacity even when applied at low doses, and displayed superior efficacy compared to extracellular vesicles carrying ACE2, in the in vitro pseudoviral assays. ACE2-VLPs were stable under different environmental temperatures, and they were effective in blocking all tested variants of concern in vitro. Finally, ACE2-VLPs displayed marked neutralization capacity against Omicron BA.1 in the Vero E6 cells. Based on their superior efficacy compared to extracellular vesicles, and their demonstrated success against live virus, ACE2-VLPs can be considered as vital candidates for treating SARS-CoV-2. This novel therapeutic approach of VLP coating with receptor particles can serve as proof-of-concept for designing effective neutralization strategies for other viral diseases in the future. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/558424v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@30ac94org.highwire.dtl.DTLVardef@1926217org.highwire.dtl.DTLVardef@165d9f0org.highwire.dtl.DTLVardef@1c737f9_HPS_FORMAT_FIGEXP M_FIG In our study, we demonstrate the prevention of SARS-CoV-2 infection through the use of Ace2-coated VLPs. C_FIG

bioengineering↗

bioRxiv2021

BRD9-containing non-canonical BAF complexes safeguard cell identity and prevent reprogramming

Epigenetic reprogramming requires extensive remodeling of chromatin landscapes to silence cell-type specific gene expression programs. ATP-dependent chromatin-remodeling complexes are important regulators of chromatin structure and gene expression; however, the role of Bromodomain-containing protein 9 (BRD9) and the associated ncBAF (non-canonical BRG1-associated factors) complex in reprogramming remains unknown. Here, we show that genetic suppression of BRD9 as well as ncBAF complex subunit GLTSCR1, but not the closely related BRD7, increase the efficiency by which induced pluripotent stem cells (iPSCs) can be generated from human somatic cells. Chemical inhibition and acute degradation of BRD9 phenocopied this effect. Interestingly, we find that BRD9 is dispensable for establishment and maintenance of human pluripotency but required for mesendodermal lineage commitment during differentiation. Mechanistically, BRD9 inhibition downregulates somatic cell type-specific genes and decreases chromatin accessibility at somatic enhancers. Collectively, these results establish BRD9 as an important safeguarding factor for somatic cell identity whose inhibition lowers chromatin-based barriers to reprogramming.

developmental biology↗

bioRxiv2020

AF10 (MLLT10) prevents somatic cell reprogramming through regulation of H3K79 methylation

The histone H3 lysine 79 (H3K79) methyltransferase DOT1L is a key chromatin-based barrier to somatic cell reprogramming. However, the mechanisms by which DOT1L safeguards cell identity and somatic-specific transcriptional programs remain unknown. Here, we employed a proteomic approach using proximity-based labeling to identify DOT1L-interacting proteins and investigated their effects on reprogramming. Among DOT1L interactors, suppression of AF10 (MLLT10) via RNA interference or CRISPR/Cas9, significantly increases reprogramming efficiency. In somatic cells and induced pluripotent stem cells (iPSCs) higher order H3K79 methylation is dependent on AF10 expression. In AF10 knockout cells, re-expression wildtype AF10, but not a mutant defective in DOT1L binding, rescues overall H3K79 methylation and reduces reprogramming efficiency. Transcriptomic analyses during reprogramming show that AF10 suppression results in downregulation of fibroblast-specific genes and accelerates the activation of pluripotency-associated genes. Our findings establish AF10 as a novel barrier to reprogramming by regulating H3K79 methylation and thereby sheds light on the mechanism by which cell identity is maintained in somatic cells.

developmental biology↗