Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling

ABSTRACT: Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling

PROVIDER: PRJNA1089941 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Cross-species cellular mapping and humanization of Fcγ receptors to advance antibody modeling

Project description:Fc receptors mediate the effector functions of therapeutic antibodies. Immunoglobulin G (IgG), the predominant antibody in circulation and clinical use, engages diverse Fc gamma (Fcγ) receptors that are expressed by multiple immune and structural cells. Here, we provide a comprehensive overview of Fcγ receptors and FcRn expression at both the transcriptomic and proteomic level in humans, macaques, and mice. We reveal species-specific differences in both Fcγ receptor diversity and cell-specific expression profile that compromise the translation of mouse and macaque preclinical models for antibody research. To overcome this, we generated a new mouse model in which human FcγRI (hCD64), FcγRIIA (hCD32A), FcγRIIB (hCD32B), FcγRIIIA (hCD16A), FcγRIIIB (hCD16B) is expressed under control of the relevant human promotors, replacing the murine counterparts (FcγRI, FcγRIIB, FcγRIII, and FcγRIV). Furthermore, to improve human antibody pharmacokinetics, murine FcRn was replaced by its human analog. We comprehensively mapped the expression of the knock-in receptors, and found that humanization led to much more faithful cell-specific Fcg receptor expression. We validated the functionality of these knock-in human receptors through in vitro and in vivo antibody-dependent cellular cytotoxicity, anaphylaxis and antigen presentation assays. This cross-species Fcγ receptor atlas and humanized mouse model with refined Fcg receptor expression and antibody pharmacokinetics will improve the preclinical assessment of antibody-based therapeutics.

2025-09-01 | GSE261975 | GEO

Tabhu: tools for antibody humanization.

Project description: Not available

| S-EPMC4308665 | biostudies-literature

Modeling Hepatoblastoma

Project description:Modeling Hepatoblastoma

| PRJNA749045 | ENA

Antibody humanization by structure-based computational protein design.

Project description: Not available

| S-EPMC5045135 | biostudies-literature

Transcription profiling of human liver biopsies from HCV associated advance disease state patients

Project description:Introduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression, using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChipâ¢ System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis. Experiment Overall Design: Liver biopsy samples were collected from patients of (a) HCV-infected early disease stage (HCV-E, control 1) (b) non-HCV advance disease stage (control 2) and (c) HCV-infected advance disease stage (HCV-A) for RNA extraction. Equal amount of RNA was pooled from samples (n=4)within each group and hybridized to HG-U133 Plus 2.0 array.

2008-06-15 | E-GEOD-7741 | biostudies-arrayexpress

Computationally driven antibody engineering enables simultaneous humanization and thermostabilization.

Project description: Not available

| S-EPMC5036863 | biostudies-literature

The Humanization and Maturation of an Anti-PrPc Antibody.

Project description: Not available

| S-EPMC10968383 | biostudies-literature

Transcription elongation can be sufficient, but is not necessary, to advance replication timing

Project description:DNA replication timing (RT) often correlates with transcription during cell fate transitions, yet notable exceptions indicate a complex relationship. Using a reductionist system in mouse embryonic stem cells, we manipulate transcriptional length and strength at a single locus upstream of the silent, late-replicating Pleiotrophin (Ptn) gene. Small reporter genes driven by two of four promoters advance RT, whereas all promoters advance RT when driving the 96-kb endogenous Ptn gene. Inducible transcription of Ptn, but not the reporter, triggers a rapid and reversible RT advance, providing a system to manipulate RT independent of differentiation. Strikingly, deletion of the Ptn promoter and enhancers abolishes transcription yet does not prevent the developmental RT switch to early replication during neural differentiation. These findings, supported by parallel genome-wide analyses during differentiation, demonstrate that transcriptional elongation can causally advance RT in a rate-dependent and context-specific manner, but that transcription is neither necessary nor sufficient for RT advancement. Our results provide a solid empirical base with which to re-evaluate decades of seemingly contradictory literature.

2026-02-01 | GSE310676 | GEO

ChIP-nexus of mineralocorticoid receptors and glucocorticoid receptors in neuroblastoma cells

Project description:ChIP-nexus of mineralocorticoid receptors and glucocorticoid receptors in neuroblastoma cells

| PRJNA474922 | ENA

Structural insights into humanization of anti-tissue factor antibody 10H10.

Project description: Not available

| S-EPMC5825201 | biostudies-literature