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<p>Human brain development spans from embryogenesis to adulthood, with dynamic gene expression controlled by cell-type-specific <i>cis</i>-regulatory element activity and three-dimensional genome organization. To advance our understanding of postnatal brain development, we simultaneously profiled gene expression and chromatin accessibility in 101,924 single nuclei from four brain regions across ten donors, covering five key postnatal stages from infancy to late adulthood. Using this dataset and chromosome conformation capture data, we constructed enhancer-based gene regulatory networks to identify cell-type-specific regulators of brain development and interpret genome-wide association study loci for ten main brain disorders. Our analysis connected 2,318 cell-specific loci to 1,149 unique genes, representing 41% of loci linked to the investigated traits, and highlighted 55 genes influencing several disease phenotypes. Pseudotime analysis revealed distinct stages of postnatal oligodendrogenesis and their regulatory programs. These findings provide a comprehensive dataset of cell-type-specific gene regulation at critical timepoints in postnatal brain development.</p>

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Multiomic single-cell profiling identifies critical regulators of postnatal brain

  • 期刊论文

  • 发表日期：

    2025年2月17日

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  • Tereza Clarence,
  • Jaroslav Bendl,
  • Xuan Cao,
  • Xinyi Wang,
  • Shiwei Zheng,
  • Gabriel E. Hoffman,
  • Alexey Kozlenkov,
  • Aram Hong,
  • Marina Iskhakova,
  • Manoj K. Jaiswal,
  • Sarah Murphy,
  • Alexander Yu,
  • Vahram Haroutunian,
  • Stella Dracheva,
  • Schahram Akbarian,
  • John F. Fullard,
  • Guo-Cheng Yuan,
  • Donghoon Lee,
  • Panos Roussos

摘要

Human brain development spans from embryogenesis to adulthood, with dynamic gene expression controlled by cell-type-specific cis-regulatory element activity and three-dimensional genome organization. To advance our understanding of postnatal brain development, we simultaneously profiled gene expression and chromatin accessibility in 101,924 single nuclei from four brain regions across ten donors, covering five key postnatal stages from infancy to late adulthood. Using this dataset and chromosome conformation capture data, we constructed enhancer-based gene regulatory networks to identify cell-type-specific regulators of brain development and interpret genome-wide association study loci for ten main brain disorders. Our analysis connected 2,318 cell-specific loci to 1,149 unique genes, representing 41% of loci linked to the investigated traits, and highlighted 55 genes influencing several disease phenotypes. Pseudotime analysis revealed distinct stages of postnatal oligodendrogenesis and their regulatory programs. These findings provide a comprehensive dataset of cell-type-specific gene regulation at critical timepoints in postnatal brain development.