Biology subjects

Morozov, K. V.

Publications and source records attributed to Morozov, K. V..

3 recordsLinked to original sources

bioRxiv2026

Accelerated Aging Signatures in 3D Genome Organization and Transcriptome in Schizophrenia

Schizophrenia is a severe neuropsychiatric disorder that affects the behavioral, emotional and cognitive state of patients. Despite its substantial heritability, the molecular etiology of the disease remains poorly understood. Many schizophrenia-associated genetic variants reside in non-coding regions, and exert their effects through distal regulatory elements of the genome. In this context, the three-dimensional organization of the genome is expected to play a decisive role in establishing contacts between these regulatory elements and their target genes, thereby mediating schizophrenia-associated dysregulation of gene expression. Here, we present a novel Hi-C dataset providing an unprecedented view of three-dimensional genome organization in post-mortem schizophrenia brain samples. Our findings indicate that most changes occur at long-range genomic distances while local architecture of topologically-associated domains remains largely intact. However, neurons display localized and functionally relevant loop differences, particularly in regulatory regions associated with neurodevelopmental processes. Global characteristics of higher-order chromatin organization show accelerated aging alteration pattern in schizophrenia, and downstream analysis of transcriptomic data in schizophrenia brain samples further confirms that schizophrenia is associated with accelerated aging.

bioinformatics↗

bioRxiv2025

Fetal signatures in the 3D genome of iPSC-derived neurons: implications for disease modeling

Induced pluripotent stem cells (iPSCs) have revolutionized neuroscience, providing an approach to generate patient-specific neurons for modeling of neurological diseases. However, it remains unclear how closely iPSC-derived neurons replicate the chromatin architecture of authentic brain neurons. Here, we uniformly process datasets for 228 human and 89 mouse Hi-C and Snm3C-seq samples of different cell subtypes merged into 96 high-coverage contact maps used to examine chromatin features ranging from chromatin compartments and topologically associating domains (TADs) to chromatin loops, Polycomb-mediated contacts, and frequently interacting regions (FIREs). We find that iPSC-derived neurons largely retain chromatin state of undifferentiated cells and resemble fetal rather than mature neurons. iPSC-derived neurons exhibit unusually strong compartmentalization, an enrichment of developmental genes at TAD borders, and a marked reduction of long-range repressive Polycomb-mediated contacts that typically silence early fetal programs. Although immature, iPSC-derived neurons offer advantages for modeling interactions between disease-associated SNPs and target genes, as many psychiatric disorders have neurodevelopmental origins. Integrating iPSC-derived and postmortem neuronal datasets therefore provides complementary insights into the chromatin landscape underlying disease-associated interactions. Our study offers a valuable Hi-C resource for the community and provides a detailed comparison of chromatin architecture throughout neuronal maturation, underscoring its importance for validating neuronal models and providing a robust framework for future studies.

genomics↗

bioRxiv2023

Extensive long-range polycomb interactions and weak compartmentalization are hallmarks of human neuronal 3D genome

Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernickes area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization. We find that genome segregation into active and inactive compartments is greatly reduced in neurons compared to other brain cells. Furthermore, neuronal Hi-C maps reveal strong long-range interactions, forming a specific network of PcG-mediated contacts in neurons that is nearly absent in other brain cells. These interacting loci contain developmental transcription factors with repressed expression in neurons and other mature brain cells. But only in neurons, they are rich in bivalent promoters occupied by H3K4me3 histone modification together with H3K27me3, which points to a possible functional role of PcG contacts in neurons. Importantly, other layers of chromatin organization also exhibit a distinct structure in neurons, characterized by an increase in short-range interactions and a decrease in long-range ones.

genomics↗