Transcriptomic alterations across various cell types in the PFC
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ABSTRACT:
PROVIDER: PRJNA1236238 | ENA |
REPOSITORIES: ENA
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Project description:Major depressive disorder (MDD) is a prevalent mental illness that significantly impacts global health, with women showing twice the prevalence of men. This study employed the chronic social defeat stress (CSDS) model in female mice to investigate cellular and molecular changes in the prefrontal cortex (PFC) associated with depressive-like behaviors. Using single-nucleus RNA sequencing (snRNA-Seq), we examined transcriptomic alterations across various cell types in the PFC. Our results revealed that interneurons exhibited the most significant transcriptomic changes among all analyzed cell types. Notably, we identified a specific subtype of interneurons, the Sox6+ interneurons (Sox6+Int), which showed a markedly increased proportion in the CSDS group. This increase was associated with enhanced inflammatory and immune responses, as well as alterations in synaptic function and mitochondrial pathways. Furthermore, we observed significant changes in cell-cell communication patterns, particularly between Sox6+Int and oligodendrocyte precursor cells (OPCs). Weighted gene co-expression network analysis (WGCNA) identified several gene modules in Sox6+Int associated with specific depressive-like behaviors, implicating pathways related to inflammation, autophagy, and synaptic function. These findings provide novel insights into the cellular and molecular mechanisms underlying MDD in females, highlighting the potential role of Sox6+Int in stress-induced depression. Our study not only extends our understanding of the neurobiological basis of depression but also identifies potential therapeutic targets for sex-specific interventions in MDD treatment.
2025-08-20 | GSE291951 | GEO
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Project description:Unraveling the cellular and molecular characteristics of human prefrontal cortex (PFC) development is crucial for understanding human cognitive abilities and vulnerability to neurological and neuropsychiatric disorders. Here, we have created a comparative repository for gene expression, chromatin accessibility, and spatial transcriptomics of human and macaque postnatal PFC development at single-cell resolution. Integrative analyses outlined species-specific dynamic trajectories of different cell types, highlighting key windows and gene regulatory networks for processes such as synaptogenesis, synaptic pruning, and gliogenesis. We identified regulatory correlates of the prolonged development of human PFC relative to macaques. Glial progenitors showed higher proliferation capability in humans compared to macaques, which was associated with distinct gene expression profiles. Furthermore, we uncovered cell types and lineages most susceptible to neurodevelopmental and neuropsychiatric disorders, focusing on transcription factors (TFs) with human-specific expression features. In summary, our discoveries shed light on human-specific regulatory programs extending postnatal cortical maturation through coordinated neuronal and glial development, with implications for cognition and neurodevelopmental disorders.
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Project description:Dual RNA-seq – sRNA profiling in various cell types
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Project description:Knockout PTENδ in mice leads to autism-like behavior pattern with increased compulsive behaviors and lack of social novelty. To further understand the in vivo function of PTENδ, we next performed RNA sequencing to characterize transcriptomic changes in the PFC from PTENδ-/- mice.
2026-06-23 | GSE325748 | GEO
Project description:RNA from various murine cell types were harvested for gene expression profiling.
2008-11-01 | E-MEXP-1802 | biostudies-arrayexpress
Project description:Maturation of the gut microbiota coincides with neurodevelopmental processes such as myelination, essential for efficient neural signal transmission. While its role in adult prefrontal cortex (PFC) myelination is known, effects on early-life myelin formation, growth, and integrity remain unclear. Here, we track gene expression in the PFC of germ-free (GF) and non-germ-free (conventional) mice. Alongside metabolomics (HP/LC) from the same region across early life development, in males and females. Metabolomics data available here <URL PLACEHOLDER> In GF mice, we observed sex- and age-dependent alterations in pathways linked to neuronal activity and myelination, with myelin-related transcriptomic changes correlating with functional shifts in neurotransmission- and metabolism-related metabolites over time. Myelin growth and integrity were also affected in a sex- and time-dependent manner. As microglia regulate neuronal activity and engulf myelin, we examined microbiota-microglia interactions and found altered expression of genes involved in microglia maturation and synaptic pruning in both species. In zebrafish larvae, the microbiota influenced the spatial distribution of microglia and oligodendrocytes within the brain and spinal cord. These findings reveal conserved microbiota-mediated modulation of neuronal activity, myelination, and glial maturation in early life, providing a foundation for future studies into these mechanisms. These files contain the RNAseq data underlying this study.
2025-12-20 | E-MTAB-16319 | biostudies-arrayexpress
Project description:Immuno-Transcriptomic Profiling Identifies Actionable Alterations in Pediatric Solid Malignancies
2021-12-07 | PXD017130 | Pride
Project description:RNA from various murine tissues or cell types was harvested for gene expression profiling.
2008-04-01 | E-MEXP-1518 | biostudies-arrayexpress
Project description:The genetics of complex disease produce alterations in molecular interactions of cellular pathways which collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer´s disease (LOAD), we constructed gene regulatory networks in hundreds of autopsied brain tissues from LOAD patients and non-demented subjects. We demonstrate that LOAD reconfigures specific portions of the molecular interaction structure, and via an integrative network-based approach we rank ordered these sub-networks (modules) for relevance to LOAD pathology, highlighting the immune/microglia module as the top ranking. Through a Bayesian inference approach we identified multiple key causal regulators for LOAD brains. Autopsied tissues from dorsolateral prefrontal cortex (PFC), visual cortex (VC) and cerebellum (CR) in brains of LOAD patients, and non-demented healthy controls, collected through the Harvard Brain Tissue Resource Center (HBTRC), were profiled on a custom-made Agilent 44K array (GPL4372_1). All subjects were diagnosed at intake and each brain underwent extensive LOAD-related pathology examination. Gene expression analyses were adjusted for age and sex, postmortem interval (PMI) in hours, sample pH and RNA integrity number (RIN). In the overall cohort of LOAD and non-demented brains the mean ± SD for sample PMI, pH and RIN were 17.8±8.3, 6.4±0.3 and 6.8±0.8, respectively. 230 samples with all PFC, VC, and CR tissue profiled were included for further multi-tissue analysis.
2013-04-25 | E-GEOD-44770 | biostudies-arrayexpress