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基因组镶嵌现象揭示了躯干神经嵴衍生神经节的发育组织。

Genomic mosaicism reveals developmental organization of trunk neural crest-derived ganglia.

作者信息

Vong Keng Ioi, Alvarez Yanina D, Noel Geoffroy, Barton Scott T, Chung Changuk, Howarth Robyn, Meave Naomi, Zhang Qingquan, Jiwani Fiza, Barrows Chelsea, Patel Arzoo, Wang Jiang Xiong, Chi Neil, Kingsmore Stephen F, White Melanie D, Yang Xiaoxu, Gleeson Joseph G

机构信息

Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA.

Rady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.

出版信息

bioRxiv. 2024 Sep 26:2024.09.25.615004. doi: 10.1101/2024.09.25.615004.

Abstract

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.

摘要

神经嵴产生多种细胞类型,但相互矛盾的结果使得其发育起源仍未得到解决。在这里,我们使用体细胞镶嵌变体作为细胞条形码,推断躯干神经嵴的胚胎克隆动态,重点关注感觉神经节和交感神经节。我们从三名成年神经典型的人类供体中,通过深度全基因组测序鉴定出1278个镶嵌变体,然后在187个解剖分离的神经节中分析等位基因比例。我们发现,感觉神经节或交感神经节特有的祖细胞克隆在头尾方向上有大量扩散,与大脑不同的是,它们呈现出强大的双侧分布。计算模型表明,神经嵴祖细胞的命运特化先于从神经管的分层。单细胞多组学分析表明,神经元和神经胶质细胞都对头尾方向的克隆组织有贡献。小鼠中的CRISPR条形码技术和鹌鹑胚胎中的活体成像证实了这些跨多个体节水平的克隆动态。我们的研究结果揭示了在外周神经节中细胞的一种进化上保守的克隆扩散。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f0/11463384/eac94df687a3/nihpp-2024.09.25.615004v1-f0001.jpg

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