Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development
Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development
Abstract The structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism—which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a single postmortem neurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo. One Sentence SummaryComprehensive evaluation of brain somatic mosaicism in the adult human identifies rules governing cellular distribution during embryogenesis.
Gleeson Joseph G.、Chai Guoliang、Pasillas Martina P.、Van Der Kraan Lucitia、Xu Xin、Breuss Martin W.、Antaki Danny、Stanley Valentina、NIMH Brain Somatic Mosaicism Network、McEvoy-Venneri Jennifer、Schlachetzki Johannes C. M.、Yang Xiaoxu、Lana Addison J.、Nahas Shareef、Nott Alexi、Cao Beibei、Nguyen An、Glass Christopher K.、Ding Yan、Newmeyer Traci Fang、Song Qiong
Department of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Cellular and Molecular Medicine, University of CaliforniaRady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Cellular and Molecular Medicine, University of CaliforniaDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Cellular and Molecular Medicine, University of CaliforniaRady Children?ˉs Institute for Genomic MedicineDepartment of Cellular and Molecular Medicine, University of CaliforniaDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Cellular and Molecular Medicine, University of California||Department of Medicine, University of CaliforniaRady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic MedicineDepartment of Neurosciences, University of California||Rady Children?ˉs Institute for Genomic Medicine
细胞生物学遗传学分子生物学
Gleeson Joseph G.,Chai Guoliang,Pasillas Martina P.,Van Der Kraan Lucitia,Xu Xin,Breuss Martin W.,Antaki Danny,Stanley Valentina,NIMH Brain Somatic Mosaicism Network,McEvoy-Venneri Jennifer,Schlachetzki Johannes C. M.,Yang Xiaoxu,Lana Addison J.,Nahas Shareef,Nott Alexi,Cao Beibei,Nguyen An,Glass Christopher K.,Ding Yan,Newmeyer Traci Fang,Song Qiong.Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2020.08.10.244814.点此复制
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