Tri-Modal Single-Cell Atlas of Developing Human Brain

DNA methylation shows persistent remodeling beyond major transcriptional and chromatin-accessibility transitions across developing human brain, enabling modality-dependent developmental clocks from 340,000 single nuclei.

• Why it matters: Regulatory layers in the developing human brain interact in ways that remain unclear, limiting understanding of how maturation shapes neuropsychiatric disease risk.
• What they did: Using ME-seq, the team profiled gene expression, chromatin accessibility, and DNA methylation in over 340,000 single nuclei from 40 specimens spanning fetal development to adolescence, then modeled developmental trajectories.
• The result: Chromatin accessibility and DNA methylation revealed partially overlapping cis-regulatory associations, while methylation-defined regions provided complementary annotations of neuropsychiatric genetic risk.

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