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Epigenomic and chromosomal architectural reconfiguration in developing human frontal cortex and hippocampus

ABSTRACT: Human frontal cortex and hippocampus play key roles in learning and cognition, and are representative structures of the six-layer neocortex and the more ancient allocortex, respectively. Here we investigated the epigenomic and 3D-chromatin conformational dynamics of human frontal cortex and hippocampus development using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation (sn-m3C-seq) generated from mid-gestational, late-gestational, infant and adult human brains. We found that the remodeling of DNA methylation predominantly happens during late-gestational to early-post-natal development, and is temporally uncoupled from the dynamics of chromatin conformation. We reconstructed regulatory hierarchies of cortical and hippocampal cell differentiation and maturation and identified brain regional-specific regulatory signatures. The single-cell 3D-regulatome approach further enabled the cell-type-specific dissection of neuropsychiatric risk loci during key neurodevelopmental stages and in adult human brains.

ORGANISM(S): Homo sapiens

PROVIDER: GSE213950 | GEO | 2022/10/07

REPOSITORIES: GEO

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