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Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE181027 | GEO | 2022/01/12

REPOSITORIES: GEO

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Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis.

Project description:Schizophrenia (SCZ) is a chronic, serious mental disorder. Although more than 200 SCZ-associated genes have been identified, the underlying molecular and cellular mechanisms remain largely unknown. Here, we generated a Setd1a (SET domain containing 1A) haploinsufficiency mouse model to understand how this SCZ-associated epigenetic factor affects gene expression in brain regions highly relevant to SCZ. Single-cell RNA sequencing revealed that Setd1a heterozygosity causes highly variable transcriptional adaptations across different cell types in prefrontal cortex (PFC) and striatum. The Foxp2+ neurons exhibit the most prominent gene expression changes among the different neuron subtypes in PFC, which correlate with changes in histone H3 lysine 4 trimethylation. Many of the genes dysregulated in Setd1a+/- mice are involved in neuron morphogenesis and synaptic function. Consistently, Setd1a+/- mice exhibit certain behavioral features of patients with SCZ. Collectively, our study establishes Setd1a+/- mice as a model for understanding SCZ and uncovers a complex brain region- and cell type-specific dysregulation that potentially underlies SCZ pathogenesis.

| S-EPMC8896793 | biostudies-literature

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [CUT&RUN]

Project description:Schizophrenia (SCZ) is a chronic, serious mental disorder with severe burden on patients’ families and society. Although over 100 genes have been linked to SCZ pathogenies, the underlying molecular and cellular mechanisms remain largely unknown. Here, we generated a Setd1a haploinsufficiency mouse model to understand how this SCZ-associated epigenetic factor affects gene expression programs in cells of brain regions highly relevant to SCZ. By comparing single-cell RNA-seq results from wild type and Setd1a+/- mice, we found Setd1a heterozygosity causes highly diverse transcriptional adaptations across different cell types in prefrontal cortex and striatum, suggesting brain region- and cell type-specific mechanisms contribute to pathophysiology of SCZ. Interestingly, we found the Foxp2+ neurons exhibit the most prominent gene expression changes among the different neuron subtypes in PFC, which correlate with the H3K4me3 changes. Importantly, many of the genes dysregulated in heterozygous Setd1a mice are linked to neuron morphogenesis and synaptic function. Consistently, heterozygous Setd1a mice exhibit certain behavioral features of SCZ patients. Collectively, our study establishes Setd1a heterozygous mice as a model for understanding SCZ and uncovers a complex brain region- and cell type-specific changes that potentially underlying SCZ pathogenesis.

2022-01-12 | GSE181025 | GEO

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [bulk RNA-seq]

2022-01-12 | GSE181024 | GEO

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [single-cell RNA-seq]

2022-01-12 | GSE181021 | GEO

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis

Project description:Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis

| PRJNA750428 | ENA

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [CUT&RUN]

Project description:Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [CUT&RUN]

| PRJNA750439 | ENA

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [bulk RNA-seq]

Project description:Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [bulk RNA-seq]

| PRJNA750433 | ENA

Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [single-cell RNA-seq]

Project description:Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis [single-cell RNA-seq]

| PRJNA750436 | ENA

Mechanism of tissue-specific functional polarization of peritoneal macrophages

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-01 | E-GEOD-56711 | biostudies-arrayexpress

Gene expression changes during Type 1 diabetes pathogenesis

Project description:This SuperSeries is composed of the SubSeries listed below. Due to privacy concerns, the SNP data is not available with unrestricted access. Refer to individual Series

2014-02-20 | E-GEOD-30211 | biostudies-arrayexpress

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