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Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development
bioRxiv - Genomics Pub Date : 2020-08-10 , DOI: 10.1101/2020.08.10.244814
Martin W. Breuss , Xiaoxu Yang , Danny Antaki , Johannes C. M. Schlachetzki , Addison J. Lana , Xin Xu , Guoliang Chai , Valentina Stanley , Qiong Song , Traci Fang Newmeyer , An Nguyen , Beibei Cao , Alexi Nott , Jennifer McEvoy-Venneri , Martina P. Pasillas , Shareef Nahas , Lucitia Van Der Kraan , Yan Ding , Christopher K. Glass , Joseph G. Gleeson ,

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.

中文翻译:

成熟大脑中的体细胞镶嵌术揭示了皮质发育过程中的克隆细胞分布

人类新皮层的结构是特定物种的基础,是复杂开发程序的反映。在这里,我们通过对大脑体细胞镶嵌症的全面评估来分析新皮层细胞谱系-作为谱系史的中性记录者。我们在25个解剖区域和三种不同模式的单个死后神经型人脑中采用了深层全基因组和变异测序,这是三种不同的方式:整体地理,分类的细胞类型和单个核。我们确定了259个镶嵌变体,揭示了定位,克隆丰度,细胞类型特异性和进化枝分布方面的显着差异。我们确定了一组分层的细胞扩散屏障,从而新皮层的左右轴分离发生在前后-和前后-腹轴分离之前。我们还发现随机分布是克隆扩散的驱动力,并且关于细胞谱系和解剖学边界的规则通常被忽略。我们的数据提供了人类大脑皮层中大脑体细胞镶嵌的全面分析,从而消除了人类胚胎中克隆分布和迁移模式的卷积。
更新日期:2020-08-11
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