@article{bibcite_7071,
  keywords = {Cell type diversity, Chromatin structure},
  author = {Camiel C. A. Mannens and Lijuan Hu and Peter L{\"o}nnerberg and Marijn Schipper and Caleb C. Reagor and Xiaofei Li and Xiaoling He and Roger A. Barker and Erik Sundstr{\"o}m and Danielle Posthuma and Sten Linnarsson},
  title = {Chromatin accessibility during human first-trimester neurodevelopment},
  abstract = {The human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene expression across the developing brain has been described at single-cell resolution1, similar atlases of chromatin accessibility have been primarily focused on the forebrain2{\textendash}4. Here we describe chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester (6{\textendash}13 weeks after conception). We defined 135 clusters and used multiomic measurements to link candidate cis-regulatory elements to gene expression. The number of accessible regions increased both with age and along neuronal differentiation. Using a convolutional neural network, we identified putative functional transcription factor-binding sites in enhancers characterizing neuronal subtypes. We applied this model to cis-regulatory elements linked to ESRRB to elucidate its activation mechanism in the Purkinje cell lineage. Finally, by linking disease-associated single nucleotide polymorphisms to cis-regulatory elements, we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being the most vulnerable to major depressive disorder-related mutations. Our findings provide a more detailed view of key gene regulatory mechanisms underlying the emergence of brain cell types during the first trimester and a comprehensive reference for future studies related to human neurodevelopment.},
  year = {2025},
  journal = {Nature},
  volume = {647},
  pages = {179-186},
  month = {2025-11},
  issn = {1476-4687},
  url = {https://www.nature.com/articles/s41586-024-07234-1},
  doi = {10.1038/s41586-024-07234-1},
  language = {en},
}