美国加州大学Joseph G. Gleeson研究小组利用体细胞嵌合体揭示了新皮质发育的克隆分布。相关论文于2022年4月20日发表于国际学术期刊《自然》杂志。
研究人员试图通过对成人人体组织进行采样来重建早期发育过程中新皮质的发生过程。通过对大脑体细胞嵌合体的全面评估，研究人员分析了人死后大脑中的新皮质克隆，这可作为中性谱系记录器。研究人员将25个不同解剖位置的采样与典型神经死亡个体的深度全基因组测序相结合，并利用从另外三个捐赠者中收集的5个样本确认了结果。研究人员从索引病例中识别出259个真正的镶嵌变体，然后对大脑和其他器官中不同的位置、细胞类型和进化枝组织进行去卷积。
研究发现，在大脑皮层中积累90-200个祖细胞后衍生的克隆倾向于形成中线轴，远在前-后轴或腹-背轴之前，这代表了前脑和后脑区域整体模式之后的二级层次结构。跨新皮质衍生细胞的克隆与来自背侧和腹侧细胞群的双重起源一致，类似于啮齿动物，而小胶质细胞谱系似乎与其他驻留脑细胞不同。该研究数据提供了对整个新皮质脑体细胞嵌合体的全面分析，并展示了人脑内的细胞起源和祖细胞分布模式。
据介绍，人新皮质结构是基本的物种特异性特征，并反映了复杂的发育过程。
附：英文原文
Title: Somatic mosaicism reveals clonal distributions of neocortical development
Author: Breuss, Martin W., Yang, Xiaoxu, Schlachetzki, Johannes C. M., Antaki, Danny, Lana, Addison J., Xu, Xin, Chung, Changuk, Chai, Guoliang, Stanley, Valentina, Song, Qiong, Newmeyer, Traci F., Nguyen, An, OBrien, Sydney, Hoeksema, Marten A., Cao, Beibei, Nott, Alexi, McEvoy-Venneri, Jennifer, Pasillas, Martina P., Barton, Scott T., Copeland, Brett R., Nahas, Shareef, Van Der Kraan, Lucitia, Ding, Yan, Glass, Christopher K., Gleeson, Joseph G.
Issue&Volume: 2022-04-20
Abstract: The structure of the human neocortex underlies species-specific traits and reflects intricate developmental programs. Here we sought to reconstruct processes that occur during early development by sampling adult human tissues. We analysed neocortical clones in a post-mortem human brain through a comprehensive assessment of brain somatic mosaicism, acting as neutral lineage recorders1,2. We combined the sampling of 25 distinct anatomic locations with deep whole-genome sequencing in a neurotypical deceased individual and confirmed results with 5 samples collected from each of three additional donors. We identified 259 bona fide mosaic variants from the index case, then deconvolved distinct geographical, cell-type and clade organizations across the brain and other organs. We found that clones derived after the accumulation of 90–200 progenitors in the cerebral cortex tended to respect the midline axis, well before the anterior–posterior or ventral–dorsal axes, representing a secondary hierarchy following the overall patterning of forebrain and hindbrain domains. Clones across neocortically derived cells were consistent with a dual origin from both dorsal and ventral cellular populations, similar to rodents, whereas the microglia lineage appeared distinct from other resident brain cells. Our data provide a comprehensive analysis of brain somatic mosaicism across the neocortex and demonstrate cellular origins and progenitor distribution patterns within the human brain.
DOI: 10.1038/s41586-022-04602-7
Source: https://www.nature.com/articles/s41586-022-04602-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
