Temporally distinct 3D multi-omic dynamics in the developing human brain
成果类型：
Article
署名作者：
Heffel, Matthew G.; Zhou, Jingtian; Zhang, Yi; Lee, Dong-Sung; Hou, Kangcheng; Pastor-Alonso, Oier; Abuhanna, Kevin D.; Galasso, Joseph; Kern, Colin; Tai, Chu-Yi; Garcia-Padilla, Carlos; Nafisi, Mahsa; Zhou, Yi; Schmitt, Anthony D.; Li, Terence; Haeussler, Maximilian; Wick, Brittney; Zhang, Martin Jinye; Xie, Fangming; Ziffra, Ryan S.; Mukamel, Eran A.; Eskin, Eleazar; Nowakowski, Tomasz J.; Dixon, Jesse R.; Pasaniuc, Bogdan; Ecker, Joseph R.; Zhu, Quan; Bintu, Bogdan; Paredes, Mercedes F.; Luo, Chongyuan
署名单位：
University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Salk Institute; University of California System; University of California San Diego; Seoul National University (SNU); Seoul National University (SNU); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California San Francisco; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California Santa Cruz; Carnegie Mellon University; Harvard University; Harvard T.H. Chan School of Public Health; University of California System; University of California San Diego; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California Los Angeles; Salk Institute; Howard Hughes Medical Institute; Salk Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
刊物名称：
Nature
ISSN/ISSBN：
0028-6340
DOI：
10.1038/s41586-024-08030-7
发表日期：
2024-11-14
关键词：
摘要：
The human hippocampus and prefrontal cortex play critical roles in learning and cognition1,2, yet the dynamic molecular characteristics of their development remain enigmatic. Here we investigated the epigenomic and three-dimensional chromatin conformational reorganization during the development of the hippocampus and prefrontal cortex, using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation generated by single-nucleus methyl-3C sequencing (snm3C-seq3)3. The remodelling of DNA methylation is temporally separated from chromatin conformation dynamics. Using single-cell profiling and multimodal single-molecule imaging approaches, we have found that short-range chromatin interactions are enriched in neurons, whereas long-range interactions are enriched in glial cells and non-brain tissues. We reconstructed the regulatory programs of cell-type development and differentiation, finding putatively causal common variants for schizophrenia strongly overlapping with chromatin loop-connected, cell-type-specific regulatory regions. Our data provide multimodal resources for studying gene regulatory dynamics in brain development and demonstrate that single-cell three-dimensional multi-omics is a powerful approach for dissecting neuropsychiatric risk loci. Using a single-nucleus multi-omics approach, a study jointly profiles the reorganization of the epigenome and the three-dimensional chromatin conformation during the development of the human hippocampus and prefrontal cortex.