{"doi":"10.1038/s41586-024-08030-7","title":"Temporally distinct 3D multi-omic dynamics in the developing human brain","abstract":"Abstract The human hippocampus and prefrontal cortex play critical roles in learning and cognition 1,2 , 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.","journal":"Nature","year":2024,"id":417802,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6257,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":37793,"name":"Jingtian Zhou","orcid":"0000-0003-2060-1922","position":1,"is_corresponding":false},{"id":1204284,"name":"Yi Zhang","orcid":"0000-0003-4380-7296","position":2,"is_corresponding":false},{"id":844140,"name":"Dong-Sung Lee","orcid":"0000-0003-3815-7057","position":3,"is_corresponding":false},{"id":311857,"name":"Kangcheng Hou","orcid":"0000-0001-7110-5596","position":4,"is_corresponding":false},{"id":628893,"name":"Oier Pastor-Alonso","orcid":"0000-0001-8075-1768","position":5,"is_corresponding":false},{"id":1204285,"name":"Kevin D. Abuhanna","orcid":"0000-0003-0994-7658","position":6,"is_corresponding":false},{"id":1204286,"name":"Joseph Galasso","orcid":"0000-0002-9013-359X","position":7,"is_corresponding":false},{"id":623702,"name":"Colin Kern","orcid":"0000-0002-3249-6405","position":8,"is_corresponding":false},{"id":1205050,"name":"Chu‐Yi Tai","orcid":null,"position":9,"is_corresponding":false},{"id":1204287,"name":"Carlos García‐Padilla","orcid":"0000-0003-2061-3157","position":10,"is_corresponding":false},{"id":1167613,"name":"Mahsa Nafisi","orcid":"0009-0005-3983-9764","position":11,"is_corresponding":false},{"id":1204288,"name":"Yi Zhou","orcid":"0000-0002-2623-8960","position":12,"is_corresponding":false},{"id":92307,"name":"Anthony D. Schmitt","orcid":"0000-0002-3818-1156","position":13,"is_corresponding":false},{"id":1204289,"name":"Terence Li","orcid":"0000-0003-4468-7361","position":14,"is_corresponding":false},{"id":24474,"name":"Maximilian Haeussler","orcid":"0000-0001-8721-8253","position":15,"is_corresponding":false},{"id":619825,"name":"Brittney Wick","orcid":null,"position":16,"is_corresponding":false},{"id":270559,"name":"Martin Jinye Zhang","orcid":"0000-0003-0006-2466","position":17,"is_corresponding":false},{"id":38370,"name":"Fangming Xie","orcid":"0000-0001-5232-1648","position":18,"is_corresponding":false},{"id":21351,"name":"Ryan Ziffra","orcid":null,"position":19,"is_corresponding":false},{"id":21452,"name":"Eran A. Mukamel","orcid":"0000-0003-3203-9535","position":20,"is_corresponding":false},{"id":15613,"name":"Eleazar Eskin","orcid":"0000-0003-1149-4758","position":21,"is_corresponding":false},{"id":21360,"name":"Tomasz J. Nowakowski","orcid":"0000-0003-2345-4964","position":22,"is_corresponding":false},{"id":81143,"name":"Jesse R. Dixon","orcid":"0000-0002-6273-2181","position":23,"is_corresponding":false},{"id":731,"name":"Bogdan Paşaniuc","orcid":"0000-0002-0227-2056","position":24,"is_corresponding":false},{"id":3799,"name":"Joseph R. Ecker","orcid":"0000-0001-5799-5895","position":25,"is_corresponding":false},{"id":623700,"name":"Quan Zhu","orcid":"0000-0001-5731-4658","position":26,"is_corresponding":false},{"id":110155,"name":"Bogdan Bintu","orcid":"0000-0001-9096-5858","position":27,"is_corresponding":false},{"id":226816,"name":"Mercedes F. Paredes","orcid":"0000-0003-2503-1447","position":28,"is_corresponding":false},{"id":29907,"name":"Chongyuan Luo","orcid":"0000-0002-8541-0695","position":29,"is_corresponding":false},{"id":1123177,"name":"Matthew G. Heffel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:56:56.807779Z","pmid":"39385032","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}