{"doi":"10.1016/j.celrep.2025.116458","title":"Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex","abstract":"The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.","journal":"Cell Reports","year":2025,"id":514608,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8421,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556244,"name":"Sonia N. 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Chhouk","orcid":null,"position":9,"is_corresponding":false},{"id":1160694,"name":"Alex Truong","orcid":null,"position":10,"is_corresponding":false},{"id":1160695,"name":"Kathleen M. Chappell","orcid":null,"position":11,"is_corresponding":false},{"id":623218,"name":"Marc Beaudin","orcid":"0000-0002-3984-3828","position":12,"is_corresponding":false},{"id":555919,"name":"Alison R. Barton","orcid":"0000-0003-0882-0196","position":13,"is_corresponding":false},{"id":558688,"name":"Shyam K. Akula","orcid":"0000-0003-2334-591X","position":14,"is_corresponding":false},{"id":849307,"name":"Yifan Zhao","orcid":"0000-0003-4829-1428","position":15,"is_corresponding":false},{"id":556242,"name":"Lariza M. Rento","orcid":"0000-0002-9361-441X","position":16,"is_corresponding":false},{"id":810338,"name":"Michael A. Lodato","orcid":"0000-0003-4175-1073","position":17,"is_corresponding":false},{"id":629581,"name":"Ryan A. Szeto","orcid":null,"position":18,"is_corresponding":false},{"id":665963,"name":"Javier Ganz","orcid":"0000-0002-2370-9819","position":19,"is_corresponding":false},{"id":857879,"name":"Pengpeng Li","orcid":"0000-0001-6653-7183","position":20,"is_corresponding":false},{"id":443846,"name":"Jessica W. Tsai","orcid":"0000-0003-0540-4330","position":21,"is_corresponding":false},{"id":496090,"name":"Robert Hill","orcid":"0000-0003-1376-0300","position":22,"is_corresponding":false},{"id":1821,"name":"Peter J. Park","orcid":"0000-0001-9378-960X","position":23,"is_corresponding":false},{"id":33029,"name":"Christopher A. Walsh","orcid":"0000-0002-0156-2238","position":24,"is_corresponding":false},{"id":69124,"name":"Vinayak V. Viswanadham","orcid":"0000-0002-0236-6490","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":null,"created_at":"2026-07-19T02:48:29.165853Z","pmid":"41240340","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":[]}